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Literature Overview CT Dual Energy imaging in Radiation Oncology

Literature Overview CT Dual Energy imaging in Radiation Oncology white paper

Literature overview CT Dual Energy imaging in Radiation Oncology An overview of the current CT Dual Energy research in Radiation Therapy and Proton Therapy (August 2020) www.siemens-healthineers.com/radiotherapy SIEMENS Healthineers The use of CT Dual Energy imaging can improve visualization for target, delineation, reduce target margins and potentially reduce variability in Radiation Therapy and Proton Therapy. This overview is based on the SOMATOM RT CT installed base and is limited to combinations of the following search parameters: “Dual Energy”, “Radiation Therapy” and “Proton Therapy”. The source for this overview is mainly: https://www.ncbi.nlm.nih.gov/pubmed/. Contents Publications on CT Dual Energy in Radiation Therapy 6 Improving structure delineation for radiation therapy planning using dual-energy CT 7 Combination of dual-energy computed tomography and iterative metal artifact reduction to increase general quality of imaging for radiotherapy patients with high dense materials. Phantom study 8 Dual-energy CT for automatic organs-at-risk segmentation in brain-tumor patients using a multi-atlas and deep-learning approach 9 Technical note: enhancing soft tissue contrast and radiation-induced image changes with dual-energy CT for radiation therapy 10 Investigating split-filter dual-energy CT for improving liver tumor visibility for radiation therapy 11 Optimal virtual monoenergetic image in “TwinBeam” dual-energy CT for organs-at-risk delineation based on contrast-noise-ratio in head-and-neck radiotherapy 12 Investigating a novel split-filter dual-energy CT technique for improving pancreas tumor visibility for radiation therapy 13 Dual-energy CT quantitative imaging: a comparison study between twin-beam and dual-source CT scanners 14 Robust quantitative contrast-enhanced dual-energy CT for radiotherapy applications 15 Dual-energy computed tomography for prediction of loco-regional recurrence after radiotherapy in larynx and hypopharynx squamous cell carcinoma 16 Assessing lung function using contrast-enhanced dual-energy computed tomography for potential applications in radiation therapy 17 Phase 1-2 Study of dual-energy computed tomography for assessment of pulmonary function in radiation therapy planning 18 A general method to derive tissue parameters for Monte Carlo dose calculation with multi-energy CT 19 2 Literature overview · CT Dual Energy imaging in Radiation Oncology Contents Initial implementation of the conversion from the energy-subtracted CT number to electron density in tissue inhomogeneity corrections: an anthropomorphic phantom study of radiotherapy treatment planning 20 Improved dose calculation accuracy for low energy brachytherapy by optimizing dual energy CT imaging protocols for noise reduction using sinogram affirmed iterative reconstruction 21 Methodological accuracy of image-based electron density assessment using dual-energy computed tomography 22 A simple formulation for deriving effective atomic numbers via electron density calibration from dual-energy CT data in the human body 23 Automatic multi-organ segmentation in dual energy CT (DECT) with dedicated 3D fully convolutional DECT networks 24 Technical note: improved CT number stability across patient size using dual-energy CT virtual monoenergetic imaging 25 Rationale and design of a prospective study on the first integrated PET/dual-energy CT system for staging and image-based radiation therapy planning of lung cancer 26 Publications on CT Dual Energy in Proton Therapy 27 Dual-energy computed tomography to assess intra- and inter-patient tissue variability for proton treatment planning of patients with brain tumor 28 Clinical feasibility of single-source dual-spiral 4D dual-energy CT for proton treatment planning within the thoracic region 29 Clinical implementation of dual-energy CT for proton treatment planning on pseudo-monoenergetic CT scans 30 Dual-energy CT based proton range prediction in head and pelvic tumor patients 31 Refinement of the Hounsfield look-up table by retrospective application of patient-specific direct proton stopping-power prediction from dual-energy CT 32 CT Dual Energy imaging in Radiation Oncology · Literature overview 3 Contents Evaluating clinical stopping power estimation from a radiotherapy dual energy CT scanner 33 Determination of proton stopping power ratio with dual-energy CT in 3D-printed tissue/air cavity surrogates 34 Monte Carlo proton dose calculations using a radiotherapy specific dual-energy CT scanner for tissue segmentation and range assessment 35 Influence of intravenous contrast agent on dose calculation in proton therapy using dual energy CT 36 A simulation study on proton computed tomography (CT) stopping power accuracy using dual energy CT scans as benchmark 37 Experimental validation of two dual-energy CT methods for proton therapy using heterogeneous tissue samples 38 The impact of dual- and multi-energy CT on proton pencil beam range uncertainties: A Monte Carlo study 39 A stoichiometric calibration method for dual energy computed tomography 40 The potential of dual-energy CT to reduce proton beam range uncertainties 41 Experimental verification of ion stopping power prediction from dual energy CT data in tissue surrogates 42 Tissue decomposition from dual energy CT data for MC based dose calculation in particle therapy 43 Technical note: improving proton stopping power ratio determination for a deformable silicone-based 3D dosimeter using dual energy CT 44 Experimental verification of stopping-power prediction from single- and dual-energy computed tomography in biological tissues 45 Comparison of single and dual energy CT for stopping power determination in proton therapy of head and neck cancer 46 4 Literature overview · CT Dual Energy imaging in Radiation Oncology Contents Evaluation of stopping-power prediction by dual- and single-energy computed tomography in an anthropomorphic ground-truth phantom 47 A comparison of relative proton stopping power measurements across patient size using dual- and single-energy CT 48 Experimental comparison of proton CT and dual energy X–ray CT for relative stopping power estimation in proton therapy 49 Comparison of proton therapy treatment planning for head tumors with a pencil beam algorithm on dual and single energy CT images 50 Systematic analysis of the impact of imaging noise on dual-energy CT-based proton stopping-power-ratio estimation 51 Comprehensive analysis of proton range uncertainties related to stopping-power-ratio estimation using dual-energy CT imaging 52 Optimal energy selection for proton stopping-power-ratio estimation using dual-energy CT-based monoenergetic imaging 53 Validation of proton stopping power ratio estimation based on dual energy CT using fresh tissue samples 54 Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy 55 Ex vivo validation of a stoichiometric dual energy CT proton stopping power ratio calibration 56 Dosimetric comparison of stopping power calibration with dual-energy CT and single-energy CT in proton therapy treatment planning 57 Status and innovations in pre-treatment CT imaging for proton therapy 58 A comparison study between single- and dual-energy CT density extraction methods for neurological proton Monte Carlo treatment planning 59 CT Dual Energy imaging in Radiation Oncology · Literature overview 5 Publications on CT Dual Energy in Radiation Therapy 6 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy Improving structure delineation for radiation therapy planning using dual-energy CT Keywords: • SOMATOM Definition AS Open • SOMATOM Drive • Author: George Noid, Justin Zhu, An Tai, Nilesh Mistry, Diane Schott, Dual Spiral Dual Energy Douglas Prah, Eric Paulson, Christopher Schultz, X. Allen Li. • Dual Source Dual Energy • Department of Radiation Oncology, Medical College of Wisconsin, Metal artifact reduction / iMAR Milwaukee, United States. (for complete affiliations see online article) • Monoenergetic / keV • Photon starvation Date: Aug 2020 • Motion artifacts Purpose: Conclusion: We present the advantages of using dual-energy CT The use of DECT for RT simulation offers clinically (DECT) for radiation therapy (RT) planning based on meaningful advantages through improved simulation our clinical experience. workflow and enhanced structure delineation for RT planning. Results: When comparing 40 keV MEIs to conventional 120-kVp CT, soft tissue contrast between the duodenum and pancreatic head was enhanced by a factor of 2.8. For a cholangio- carcinoma patient, contrast between tumor and surroun- ding tissue was increased by 96 HU and contrast-to-noise ratio was increased by up to 60% for 40 keV MEIs compared to conventional CT. Simultaneous dual-source DECT also preserved spatial resolution in comparison to sequential DECT as evidenced by the identification of vasculature in a pancreas patient. Volume of artifacts for five patients with titanium implants was reduced by over 95% for 190 keV MEIs compared to 120-kVp CT images. A 367-cm3 region of photon starvation was identified by low CT numbers in the soft tissue of a mantle patient in a conventional CT scan but was eliminated in a 190 keV MEI. Fat maps enhanced image contrast as demonstrated by a meningioma patient. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484725/ CT Dual Energy imaging in Radiation Oncology · Literature overview 7 Publications on CT Dual Energy in Radiation Therapy Combination of dual-energy computed tomography and iterative metal artifact reduction to increase general quality Keywords: of imaging for radiotherapy patients with high dense • SOMATOM Definition AS materials. Phantom study • Dual Spiral Dual Energy • Metal artifact reduction / iMAR • Monoenergetic / keV Author: Bartosz Pawałowski, Rafał Panek, Hubert Szweda, Tomasz Piotrowski Department of Medical Physics, Greater Poland Cancer Centre, Poznań, Poland. (for complete affiliations see online article) Date: Aug 2020 Purpose: Conclusion: To evaluate the use of pseudo-monoenergetic reconstruc- The use of 70 keV PMR with iMAR allows for significant tions (PMR) from dual-energy computed tomography, metal artifact reduction and low CT number errors combined with the iterative metal artifact reduction observed in the vicinity of dense materials. It is therefore (iMAR) method. an attractive alternative to high keV imaging when imaging patients with metallic implants, especially in the Methods: context of radiotherapy planning. Pseudo-monoenergetic CT images were obtained using the dual-energy mode on the Siemens Somatom Definition AS scanner. A range of PMR combinations (70-130 keV) were used with and without iMAR. A Virtual Water™ phantom was used for quantitative assessment of error in the presence of high density materials: titanium, alloys 330 and 600. The absolute values of CT number differences (AD) and normalised standard deviations (NSD) were calculated for different phantom positions. Image quality was assessed using an anthropomorphic pelvic phantom with an embedded hip prosthesis. Image quality was scored blindly by five observers. https://pubmed.ncbi.nlm.nih.gov/32818774/ 8 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy Dual-energy CT for automatic organs-at-risk segmentation in brain-tumor patients using a multi-atlas and Keywords: deep-learning approach • SOMATOM Definition AS • Dual Spiral Dual Energy • Author: van der Heyden B, Wohlfahrt P, Eekers DBP, Richter C, Terhaag K, syngo.via RT Image Suite Troost EGC, Verhaegen F. • Contouring / Delineation • Department of Radiation Oncology (MAASTRO), Multi-atlas or Deep-learning Maastricht University Medical Centre, Maastricht, Netherlands. • Monoenergetic / keV (for complete affiliations see online article) • Dose calculation • SAFIRE Date: Mar 2019 Abstract: In radiotherapy, computed tomography (CT) datasets are dual-energy CT (DECT) datasets, which have been shown mostly used for radiation treatment planning to achieve to improve the image quality compared to conventional a high-conformal tumor coverage while optimally sparing 120 kVp single-energy CT. In this study, the performance healthy tissue surrounding the tumor, referred to as of an in-house developed MA and a DL method (two-step organs-at-risk (OARs). Based on CT scan and/or magnetic three-dimensional U-net) was quantitatively and resonance images, OARs have to be manually delineated qualitatively evaluated on various DECT-derived pseudo- by clinicians, which is one of the most time-consuming monoenergetic CT datasets ranging from 40 keV to tasks in the clinical workflow. Recent multi-atlas (MA) 170 keV. At lower energies, the MA method resulted in or deep-learning (DL) based methods aim to improve more accurate OAR segmentations. Both the qualitative the clinical routine by an automatic segmentation of OARs and quantitative metric analysis showed that the DL on a CT dataset. However, so far no studies investigated approach often performed better than the MA method. the performance of these MA or DL methods on https://www.ncbi.nlm.nih.gov/pubmed/30858409 CT Dual Energy imaging in Radiation Oncology · Literature overview 9 Publications on CT Dual Energy in Radiation Therapy Technical note: enhancing soft tissue contrast and radiation-induced image changes with dual-energy CT Keywords: for radiation therapy • SOMATOM Definition AS Open • Dual Spiral Dual Energy • Author: Noid G, Tai A, Schott D, Mistry N, Liu Y, Gilat-Schmidt T, Robbins J, Li X Monoenergetic / keV • Contrast-to-noise ratio / CNR Department of Radiation Oncology, Medical College of Wisconsin, • Milwaukee, USA. (for complete affiliations see online article) Contouring / Delineation • Pancreatic cancer Date: Jul 2018 Purpose: Conclusion: The purpose of this work is to investigate the use of Low-energy monoenergetic decompositions from DECT low-energy monoenergetic decompositions obtained substantially increase soft tissue contrast and increase from dual-energy CT (DECT) to enhance image contrast the magnitude of radiation-induced changes in CT and the detection of radiation-induced changes of CT histogram textures during RT delivery for pancreatic textures in pancreatic cancer. cancer. Therefore, quantitative DECT may assist the detection of early RT response. Results: Data of monoenergetic decompositions of the 10 patients confirmed the expected enhancement of soft tissue contrast as the energy is decreased. The changes in the selected CT histogram features in the pancreas during RT delivery were amplified with the low-energy mono- energetic decompositions, as compared to the changes measured from the 120 kVp CTs. For the patients studied, the average reduction in the MCTN in pancreas from the first to the last (the 28th) treatment fraction was 4.09 HU for the standard 120 kVp and 11.15 HU for the 40 keV monoenergetic decomposition. https://pubmed.ncbi.nlm.nih.gov/29972868/ 10 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy Investigating split-filter dual-energy CT for improving liver tumor visibility for radiation therapy Keywords: • SOMATOM Definition Edge • TwinBeam Dual Energy • Author: Lianna D. DiMaso, Jessica R. Miller, Michael J. Lawless, Monoenergetic / keV Michael F. Bassetti, Larry A. DeWerd, Jessie Huang. • Contrast-to-noise ratio / CNR • Department of Medical Physics, University of Wisconsin-Madison, Madison, USA. Virtual Non Contrast / VNC (for complete affiliations see online article) • Contrast / Iodine • Contouring / Delineation Date: Oct 2019 • Liver tumor visibility Purpose: Conclusion: Accurate liver tumor delineation is crucial for radiation Liver tumor contrast was significantly improved using therapy, but liver tumor volumes are difficult to visualize split-filter DECT 40 keV VMIs compared to mixed images. with conventional single-energy CT. This work investigates On average, there was no statistical difference in CNR the use of split-filter dual-energy CT (DECT) for liver tumor between the mixed images and VMIs, but for individual visibility by quantifying contrast and contrast-to-noise cases, CNR was greatly increased for the 57 keV and ratio (CNR). 40 keV VMIs. Therefore, although not universally successful for our patient cohort, split-filter DECT VMIs may provide Results: substantial gains in tumor visibility of certain liver cases For the arterial phase, liver GTV contrast was 12.1 ± 10.0 HU for radiation therapy treatment planning. and 43.1 ± 32.3 HU (P < 0.001) for the mixed images and 40 keV VMIs. Image noise increased on average by 116% for the 40 keV VMIs compared to the mixed images. The average CNR did not change significantly (1.6 ± 1.5, 1.7 ± 1.4, 2.4 ± 1.7 for the mixed, 57 keV and 40 keV VMIs (P > 0.141)). For individual cases, however, CNR increases of up to 607% were measured for the 40 keV VMIs compared to the mixed image. Venous phase 40 keV VMIs demonstrated an average increase of 35.4 HU in GTV contrast and 121% increase in image noise. Average CNR values were also not statistically different, but for individual cases CNR increases of up to 554% were measured for the 40 keV VMIs compared to the mixed image. https://pubmed.ncbi.nlm.nih.gov/32410336/ CT Dual Energy imaging in Radiation Oncology · Literature overview 11 Publications on CT Dual Energy in Radiation Therapy Optimal virtual monoenergetic image in “TwinBeam” dual-energy CT for organs-at-risk delineation based on Keywords: contrast-noise-ratio in head-and-neck radiotherapy • SOMATOM Definition Edge • TwinBeam Dual Energy • Author: Wang T, Ghavidel BB, Beitler JJ, Tang X, Lei Y, Curran WJ, Contrast-to-noise ratio / CNR Liu T, Yang X. • Monoenergetic / keV • Department of Radiation Oncology and Winship Cancer Institute, Virtual Non Contrast / VNC Emory University, Atlanta, USA. (for complete affiliations see online article) • Contrast / Iodine • Contouring / Delineation Date: Jan 2019 • Dose calculation • Head and neck Purpose: Conclusion: Dual-energy computed tomography (DECT) using We have proposed a clinically feasible protocol that selects TwinBeam CT (TBCT) is a new option for radiation oncology the optimal energy level of the virtual monoenergetic image simulators. TBCT scanning provides virtual monoenergetic in TBCT for OAR delineation based on the CNR in head-and- images which are attractive in treatment planning since neck OAR. This protocol can be applied in TBCT simulation. lower energies offer better contrast for soft tissues, and higher energies reduce noise. A protocol is needed to achieve optimal performance of this feature. In this study, we investigated the TBCT scan schema with the head- and-neck radiotherapy workflow at our clinic and selected the optimal energy with best contrast-noise-ratio (CNR) in organs-at-risks (OARs) delineation for head-and-neck treatment planning. Results: Computed tomography scans of ten patients by TBCT were used to test the optimal monoenergetic image for the CNR of OAR. Based on the maximized CNR, the optimal energy values were 78.5 ± 5.3 keV for the brainstem, 78.0 ± 4.2 keV for the mandible, 78.5 ± 5.7 keV for the parotid glands, and 78.5 ± 5.3 keV for the spinal cord. Overall, the optimal energy for the maximum CNR of these OARs in head-and-neck cancer patients was 80 keV. https://www.ncbi.nlm.nih.gov/pubmed/30693665 12 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy Investigating a novel split-filter dual-energy CT technique for improving pancreas tumor visibility Keywords: for radiation therapy • SOMATOM Definition Edge • TwinBeam Dual Energy • Author: Di Maso LD, Huang J, Bassetti MF, DeWerd LA, Miller JR. Monoenergetic / keV • Contrast-to-noise ratio / CNR Department of Medical Physics, University of Wisconsin-Madison, Madison, USA. • (for complete affiliations see online article) Virtual Non Contrast / VNC • Contrast / Iodine Date: Sept 2018 • Contouring / Delineation • Dose calculation • Pancreas tumor visibility Purpose: Conclusion: Tumor delineation using conventional CT images can be Pancreatic tumor contrast and CNR were significantly a challenge for pancreatic adenocarcinoma where contrast improved using VMIs reconstructed from the split-filter between the tumor and surrounding healthy tissue is low. DECT technique, and the use of iterative reconstruction This work investigates the ability of a split-filter dual- further improved CNR. This gain in tumor contrast may energy CT (DECT) system to improve pancreatic tumor lead to more accurate tumor delineation for radiation contrast and contrast-to-noise ratio (CNR) for radiation therapy treatment planning. therapy treatment planning. Results: The VMIs at 40 keV had a 110% greater image noise compared to the mixed 120 kVp-equivalent images (P < 0.0001). VMIs at 40 keV increased GTV contrast from 15.9 ± 19.9 HU to 93.7 ± 49.6 HU and CNR from 1.37 ± 2.05 to 3.86 ± 2.78 in comparison to the mixed 120 kVp-equivalent images. The iterative reconstruction algorithm investigated decreased noise in the VMIs by about 20% and improved CNR by about 30%. https://www.ncbi.nlm.nih.gov/pubmed/30117641 CT Dual Energy imaging in Radiation Oncology · Literature overview 13 Publications on CT Dual Energy in Radiation Therapy Dual-energy CT quantitative imaging: a comparison study between twin-beam and dual-source CT scanners Keywords: • SOMATOM Definition Edge • SOMATOM Force Author: Almeida I, Schyns L, Öllers M, van Elmpt W, Parodi K, Landry G, • SOMATOM Definition Flash Verhaegen F • syngo.via • Department of Radiation Oncology (MAASTRO), TwinBeam Dual Energy Maastricht University Medical Centre, the Netherlands. • Dual Source Dual Energy (for complete affiliations see online article) • Effective atomic number • Relative electron density Date: Jan 2017 • Contrast / Iodine • Contrast-to-noise ratio / CNR Purpose: Conclusion: To assess image quality and to quantify the accuracy Spatial resolution is similar for the three scanners. of relative electron densities (ρe ) and effective atomic The twin-beam is able to derive ρe and Zeff, but with numbers (Zeff) for three dual-energy computed tomography inferior accuracy compared to both dual-source scanners. (DECT) scanners: a novel single-source split-filter (i.e., twin-beam) and two dual-source scanners. Results: The third-generation scanners have an image resolution of 6.2, ~0.5 lp/cm higher than the second generation scanner. The twin-beam scanner has low imaging contrast for iodine materials due to its limited spectral separation. The parameterization methods resulted in calibrations with low fit residuals for the dual-source scanners, yielding values of ρe and Zeff close to the reference values (errors within 1.2% for ρe and 6.2% for Zeff for a dose of 20 mGy, excluding lung substitute tissues). The twin- beam scanner presented overall higher errors (within 3.2% for ρe and 28% for Zeff, also excluding lung inserts) and also larger variations for uniform inserts. https://pubmed.ncbi.nlm.nih.gov/28070917/ 14 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy Robust quantitative contrast-enhanced dual-energy CT for radiotherapy applications Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Lapointe A, Lalonde A, Bahig H, Carrier JF, Bedwani S, Bouchard H. Virtual Non Contrast / VNC • Contrast / Iodine Département de physique, Université de Montréal, Montréal, Canada. • (for complete affiliations see online article) Electron Density • Contouring / Delineation Date: May 2018 • Dose calculation • Material decomposition Purpose: Conclusion: The purpose of this study was to develop and validate This study identifies two accurate methods to quantify accurate methods for determining iodine content and iodine-based contrast agents and virtual non-contrast virtual non-contrast maps of physical parameters, such composition images with dual-energy CT. One is the as electron density, in the context of radiotherapy. two-material decomposition with a priori knowledge of the constituent components focused on organ-specific Results: applications, such as kidney or lung function assessment. Results show that in the case of known a priori on The other method is the eigentissue decomposition and the composition of the targeted tissue, the two-material is useful for general radiotherapy applications, such as decomposition is robust to variable densities and atomic treatment planning where accurate dose calculations are compositions without biasing the results. In the absence needed in the absence of contrast agent. of a priori knowledge on the target tissue composition, the eigentissue decomposition method yields minimal bias and higher robustness to variations. Results from the experimental calibration and the images of two patients show that the extracted quantities are accurate and the bias is negligible for both methods with respect to clinical applications in their respective scope of use. For the patient imaged with a contrast agent, virtual non- contrast electron densities are found in good agreement with values extracted from the scan without contrast agent. https://www.ncbi.nlm.nih.gov/pubmed/29697145 CT Dual Energy imaging in Radiation Oncology · Literature overview 15 Publications on CT Dual Energy in Radiation Therapy Dual-energy computed tomography for prediction of loco-regional recurrence after radiotherapy in larynx Keywords: and hypopharynx squamous cell carcinoma • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Bahig H, Lapointe A, Bedwani S, de Guise J, Lambert L, Filion E, Monoenergetic / keV Roberge D, Létourneau-Guillon L, Blais D, Ng SP, Nguyen-Tan PF • Contrast / Iodine • Radiation Oncology Department, Centre Hospitalier de l’Université de Montréal, Contouring / Delineation Montreal, Canada. (for complete affiliations see online article) • Larynx and Hypopharynx Date: Jan 2019 Purpose: Conclusion: To investigate the role of quantitative pre-treatment dual- This exploratory study suggests that pre-radiotherapy energy computed tomography (DECT) for prediction of DECT-derived IC quantitative analysis of tumoral volume loco-regional recurrence (LRR) in patients with larynx/ may help predict LRR in L/H SCC. hypopharynx squamous cell cancer (L/H SCC). Results: Twenty-five patients, including 20 supraglottic and 5 pyriform sinus tumors were analysed. Stage I, II, III, IVa and IVb constituted 4% (1 patient), 24%, 36%, 28% and 8% of patients, respectively; 44% had concurrent chemo- radiotherapy and 28% had neodjuvant chemotherapy. Median follow-up was 21 months. Locoregional control at 1 and 2 years were 75% and 69%, respectively. For the entire cohort, GTVn volume (HR 1.177 [1.001-1.392], p = 0.05), voxel-based maximum IC of GTVp (HR 1.099 [95% CI: 1.001-1.209], p=0.05) and IC standard deviation of GTVn (HR 9.300 [95% CI: 1.113-77.725] p = 0.04) were predictive of LRR. On subgroup analysis of patients treated with upfront radiotherapy +/- chemotherapy, both voxel- based maximum IC of GTVp (HR 1.127 [95% CI: 1.010- 1.258], p = 0.05) and IC kurtosis of GTVp (HR 1.088 [95% CI: 1.014-1.166], p = 0.02) were predictive of LRR. https://www.ncbi.nlm.nih.gov/pubmed/30599844 16 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy Assessing lung function using contrast-enhanced dual-energy computed tomography for potential Keywords: applications in radiation therapy • SOMATOM Definition Flash • Dual Source Dual Energy Author: Lapointe A, Bahig H, Blais D, Bouchard H, Filion É, Carrier JF, • Contrast / Iodine Bedwani S. • Contouring / Delineation • Département de physique, Université de Montréal, Montréal, Canada. Functional imaging (for complete affiliations see online article) • Lung / Free breathing • 4DCT Date: Oct 2017 Purpose: Conclusion: There is an increasing interest in the evaluation of lung The extraction of iodine concentration maps from function from physiological images in radiation therapy a contrast-enhanced DECT scan is achieved to compute treatment planning to reduce the extent of post-radiation the differential function for each lung subvolume and toxicities. The purpose of this work was to retrieve reliable good agreement is found in respect to SPECT/CT. One functional information from contrast-enhanced dual- promising avenue in radiation therapy is to include such energy computed tomography (DECT) for new applications functional information during treatment planning dose in radiation therapy. The functional information obtained optimization to spare functional lung tissues. by DECT is also compared with other methods using single-energy CT (SECT) and single-photon emission computed tomography (SPECT) with CT. The differential function between left and right lung, as well as between lobes is computed for all methods. Results: The differential function per lobe derived from SPECT/CT correlates strongly with DECT (Pearson’s coefficient r = 0.91) and moderately with SECT (r = 0.46). The differential function for the left lung shows a mean difference of 7% between SPECT/CT and DECT; and 17% between SPECT/CT and SECT. The presence of nonfunctional areas, such as localized emphysema or a lung tumor, is reflected by an intensity drop in the iodine concentration maps. Functional dose volume histograms (fDVH) are also generated for two patients as a proof of concept. https://www.ncbi.nlm.nih.gov/pubmed/28718888 CT Dual Energy imaging in Radiation Oncology · Literature overview 17 Publications on CT Dual Energy in Radiation Therapy Phase 1-2 Study of dual-energy computed tomography for assessment of pulmonary function in radiation Keywords: therapy planning • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Bahig H, Campeau MP, Lapointe A, Bedwani S, Roberge D, de Guise J, Contrast / Iodine Blais D, Vu T, Lambert L, Chartrand-Lefebvre C, Lord M, Filion E. • Pulmonary function • Radiation Oncology Department, Centre Hospitalier de l’Université de Montréal, 4DCT Montreal, Canada. (for complete affiliations see online article) Date: Oct 2017 Purpose: Conclusion: To quantify lung function according to a dual-energy Lobar function derived from a DECT iodine map correlates computed tomography (DECT)-derived iodine map in well with SPECT/CT, and its integration in lung treatment patients treated with radiation therapy for lung cancer, planning is associated with significant differences in V5 and to assess the dosimetric impact of its integration and MLD to functional lungs. Future work will involve in radiation therapy planning. integration of the weighted functional volume in the treatment planning system, along with integration Results: of an iodine map for functional lung-sparing IMRT. Twenty-five patients with lung cancer, including 18 patients treated with stereotactic ablative radiation therapy and 7 patients with intensity modulated radiation therapy (locally advanced), were included. Eighty-four percent had chronic obstructive pulmonary disease. Median (range) forced expiratory volume in 1 second was 62% of predicted (29%-113%), and median diffusing capacity of the lung for carbon monoxide was 56% (39%-91%). There was a strong linear correlation between DECT- and SPECT/ CT-derived lobar function (Pearson coefficient correlation r=0.89, P<.00001). Mean (range) differences in V5, V20, and MLD between anatomic and functional lung volumes were 16% (0%-48%, P=.03), 5% (1%-15%, P=.12), and 15% (1%-43%, P=.047), respectively. https://www.ncbi.nlm.nih.gov/pubmed/28871983 18 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy A general method to derive tissue parameters for Monte Carlo dose calculation with multi-energy CT Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Lalonde A, Bouchard H. Dose calculation • Electro Density Département de Physique, Université de Montréal, Pavillon Roger-Gaudry, Montréal, Canada. (for complete affiliations see online article) Date: Nov 2016 Abstract: To develop a general method for human tissue the water-lipid-protein material decomposition and characterization with dual- and multi-energy CT and comparable to the parameterization technique. In deter- evaluate its performance in determining elemental mining proton stopping powers and energy absorption compositions and quantities relevant to radiotherapy coefficients with dual-energy CT, the method generally Monte Carlo dose calculation. Ideal materials to describe shows better accuracy and unbiased results. The generality human tissue are obtained applying principal component of the method is demonstrated simulating multi-energy analysis on elemental weight and density data available CT data to show the potential to extract more information in literature. The theory is adapted to elemental with multiple energies. The method proposed in this composition for solving tissue information from CT data. paper shows good performance to determine elemental A novel stoichiometric calibration method is integrated to compositions from dual-energy CT data and physical the technique to make it suitable for a clinical environment. quantities relevant to radiotherapy dose calculation. The performance of the method is compared with two The method is particularly suitable for Monte Carlo techniques known in literature using theoretical CT data. calculations and shows promise in using more than two In determining elemental weights with dual-energy CT, energies to characterize human tissue with CT. the method is shown to be systematically superior to https://www.ncbi.nlm.nih.gov/pubmed/27779137 CT Dual Energy imaging in Radiation Oncology · Literature overview 19 Publications on CT Dual Energy in Radiation Therapy Initial implementation of the conversion from the energy- subtracted CT number to electron density in tissue Keywords: inhomogeneity corrections: an anthropomorphic • SOMATOM Definition Flash phantom study of radiotherapy treatment planning • Dual Source Dual Energy • Electron density • Dosimetry Author: Tsukihara M, Noto Y, Sasamoto R, Hayakawa T, Saito M. • Dose volume analysis Division of Radiological Technology, Niigata University, Japan. • Standards and calibration (for complete affiliations see online article) Date: Mar 2015 Purpose: To achieve accurate tissue inhomogeneity corrections calibrations. In contrast, the dose distributions and DVHs in radiotherapy treatment planning, the authors had of the body-EDP and head-EDP calibrations coincided with previously proposed a novel conversion of the energy- each other almost perfectly in the ΔHU-ρ(e) conversion subtracted computed tomography (CT) number to an for 100-140 kV/Sn. The difference between the V100’s electron density (ΔHU-ρ(e) conversion), which provides (the mean planning target volume receiving 100% of a single linear relationship between ΔHU and ρ(e) over the prescribed dose; a DVH parameter) of the body-EDP a wide range of ρ(e). The purpose of this study is to and head-EDP calibrations could be reduced to less than present an initial implementation of the ΔHU-ρ(e) 1% using the ΔHU-ρ(e) conversion, but exceeded 11% conversion method for a treatment planning system for the HU-ρ(e) conversion. (TPS). In this paper, two example radiotherapy plans are used to evaluate the reliability of dose calculations Conclusion: in the ΔHU-ρ(e) conversion method. The ΔHU-ρ(e) conversion can be implemented for currently Results: available TPS’s without any modifications or extensions. The ΔHU-ρ(e) conversion appears to be a promising method In both treatment plans, the performance of the ΔHU-ρ(e) for providing an accurate and reliable inhomogeneity conversion was superior to that of the conventional correction in treatment planning for any ill-conditioned HU-ρ(e) conversion in terms of the reliability of dose scans that include (i) the use of a calibration EDP that is calculations. Especially, for the oral tumor plan, which nonequivalent to the patient’s body tissues, (ii) a mismatch dealt with dentition and bony structures, treatment between the size of the patient and the calibration EDP, planning with the HU-ρ(e) conversion exhibited apparent or (iii) a large quantity of high-density and high-atomic- discrepancies between the dose distributions and dose- number tissue structures. volume histograms (DVHs) of the body-EDP and head-EDP https://www.ncbi.nlm.nih.gov/pubmed/25735292 20 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy Improved dose calculation accuracy for low energy brachytherapy by optimizing dual energy CT imaging Keywords: protocols for noise reduction using sinogram affirmed • SOMATOM Definition Flash iterative reconstruction • Dual Source Dual Energy • Safire • Brachytherapy Author: Landry G, Gaudreault M, van Elmpt W, Wildberger J, Verhaegen F. • Dose calculation Department of Radiation Oncology (MAASTRO), University Medical Center, Maastricht, the Netherlands. (for complete affiliations see online article) Date: Feb 2015 Abstract: The goal of this study was to evaluate the noise Standard deviations for Zeff and ρe were reduced up to a reduction achievable from dual energy computed factor ∼2 when using SAFIRE with strength 5 compared tomography (CT) imaging (DECT) using filtered to FBP. Standard deviations on Zeff and ρe as low as 0.15 backprojection (FBP) and iterative image reconstruction and 0.006 were achieved for the muscle insert algorithms combined with increased imaging exposure. representing typical soft tissue using a CTDIvol of 40 mGy We evaluated the data in the context of imaging for and 3 mm slice thickness. Dose calculation accuracy was brachytherapy dose calculation, where accurate generally improved when using SAFIRE. Mean (maximum quantification of electron density ρe and effective atomic absolute) dose errors of up to 1.3% (21%) with FBP were number Zeff is beneficial. reduced to less than 1% (6%) with SAFIRE at a CTDIvol of A dual source CT scanner was used to scan a phantom 10 mGy. Using a CTDIvol of 40mGy and SAFIRE yielded containing tissue mimicking inserts. DECT scans were mean dose calculation errors of the order of 0.6% which acquired at 80 kVp/140Sn kVp (where Sn stands for tin was the MC dose calculation precision in this study and filtration) and 100 kVp/140Sn kVp, using the same values no error was larger than ±2.5% as opposed to errors of of the CT dose index CTDIvol for both settings as a up to -4% with FBP. measure for the radiation imaging exposure. Four CTDIvol This phantom study showed that the SAFIRE image levels were investigated. Images were reconstructed reconstruction algorithm provided reduced standard using FBP and sinogram affirmed iterative reconstruction deviations of Zeff and ρe in uniform regions of interest (SAFIRE) with strength 1,3 and 5. From DECT scans two while preserving mean Zeff and ρe values. This resulted material quantities were derived, Zeff and ρe DECT images in improved material type assignment. The use of SAFIRE . were used to assign material types and the amount of improved brachytherapy dose calculations for the materials improperly assigned voxels was quantified for each from the phantom investigated in this study using 125I. protocol. The dosimetric impact of improperly assigned voxels was evaluated with Geant4 Monte Carlo (MC) dose calculations for an 125I source in numerical phantoms. https://pubmed.ncbi.nlm.nih.gov/26422576/ CT Dual Energy imaging in Radiation Oncology · Literature overview 21 Publications on CT Dual Energy in Radiation Therapy Methodological accuracy of image-based electron density assessment using dual-energy computed tomography Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Möhler C, Wohlfahrt P, Richter C, Greilich S. Effective atomic number • Electron density German Cancer Research Center (DKFZ), Heidelberg, Germany. • (for complete affiliations see online article) Monoenergetic / keV Date: May 2017 Purpose: in the calibration result in spite of different experimental Electron density is the most important tissue property setups and CT protocols used. Employing a general influencing photon and ion dose distributions in calibration per scanner type and voltage combination radiotherapy patients. Dual-energy computed tomography is thus conceivable. (DECT) enables the determination of electron density by combining the information on photon attenuation Conclusion: obtained at two different effective x-ray energy spectra. Given the high suitability for clinical application of the Most algorithms suggested so far use the CT numbers alpha-blending approach in combination with a very provided after image reconstruction as input parameters, small methodological uncertainty, we conclude that i.e., are imaged-based. To explore the accuracy that can be further refinement of image-based DECT-algorithms achieved with these approaches, we quantify the intrinsic for electron density assessment is not advisable. methodological and calibration uncertainty of the seemingly simplest approach. Results: Analyzing calculated spectrally weighted attenuation coefficients, we find universal applicability of the investigated approach to arbitrary mixtures of human tissue with an upper limit of the methodological uncertainty component of 0.2%, excluding high-Z elements such as iodine. The proposed calibration procedure is bias-free and straightforward to perform using standard equipment. Testing the calibration on five published data sets, we obtain very small differences https://pubmed.ncbi.nlm.nih.gov/28397977/ 22 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy A simple formulation for deriving effective atomic numbers via electron density calibration from dual-energy CT data Keywords: in the human body • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Saito M, Sagara S. syngo.via • Effective atomic number Department of Radiological Technology, Faculty of Medicine, • Niigata University, Japan. (for complete affiliations see online article) Electron density Date: May 2017 Purpose: Conclusion: The main objective of this study is to propose a simple The DEEDZ conversion method based on the simple formulation (which we called DEEDZ) for deriving formulation proposed could facilitate the construction of effective atomic numbers (Zeff) via electron density (ρe) ρe and Zeff images from acquired DECT data. calibration from dual-energy (DE) CT data. We carried out numerical analysis of this DEEDZ method for a large variety of materials with known elemental compositions and mass densities using an available photon cross sections database. The new conversion approach was also applied to previously published experimental DECT data to validate its practical feasibility. Results: The simulated Zeff ‘s were in excellent agreement with the reference values for almost all of the ICRU-46 human tissues over the Zeff range from 5.83 (gallstones- cholesterol) to 16.11 (bone mineral-hydroxyapatite). The relative deviations from the reference Zeff were within ± 0.3% for all materials, except for one outlier that presented a -3.1% deviation, namely, the thyroid. The reason for this discrepancy is that the thyroid contains a small amount of iodine, an element with a large atomic number (Z = 53). In the experimental case, we confirmed that the simple formulation with less fit parameters enable to calibrate Zeff as accurately as the existing calibration procedure. https://pubmed.ncbi.nlm.nih.gov/28236659/ CT Dual Energy imaging in Radiation Oncology · Literature overview 23 Publications on CT Dual Energy in Radiation Therapy Automatic multi‐organ segmentation in dual energy CT (DECT) with dedicated 3D fully convolutional Keywords: DECT networks • SOMATOM Force • Dual Source Dual Energy • Author: Chen S, Zhong X, Hu S, Dorn S, Kachelrieß M, Lell M, Maier A. Contouring / Delineation • Deep learning Pattern Recognition Lab, Universität Erlangen-Nürnberg, Erlangen, Germany. • (for complete affiliations see online article) Thorax/abdomen Date: Dec 2019 Purpose: respectively. The network architectures exploit dual-energy Dual-energy computed tomography (DECT) has shown spectra and outperform deep learning for SECT. great potential in many clinical applications. By incorpo- rating the information from two different energy spectra, Conclusion: DECT provides higher contrast and reveals more material The results of the cross-validation show that our methods differences of tissues compared to conventional single- are feasible and promising. Successful tests on special energy CT (SECT). Recent research shows that automatic clinical cases reveal that our methods have high multi-organ segmentation of DECT data can improve DECT adaptability in the practical application. clinical applications. However, most segmentation methods are designed for SECT, while DECT has been significantly less pronounced in research. Therefore, a novel approach is required that is able to take full advantage of the extra information provided by DECT. Results: Quantitative evaluation using 45 thorax/abdomen DECT datasets acquired with a clinical dual-source CT system was investigated. The segmentation of six thoracic and abdominal organs (left and right lungs, liver, spleen, and left and right kidneys) were evaluated using a fivefold cross-validation strategy. In all of the tests, we achieved the best average Dice coefficients of 98% for the right lung, 98% for the left lung, 96% for the liver, 92% for the spleen, 95% for the right kidney, 93% for the left kidney, https://pubmed.ncbi.nlm.nih.gov/31816095/ 24 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Radiation Therapy Technical note: improved CT number stability across patient size using dual-energy CT virtual monoenergetic imaging Keywords: • SOMATOM Force • Dual Source Dual Energy • Author: Michalak G, Grimes J, Fletcher J, Halaweish A, Lifeng Y, Leng S, CARE Dose4D McCollough C. • Monoenergetic / keV • Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA. Improved CT number stability (for complete affiliations see online article) Date: Jan 2016 Purpose: Conclusion: The purpose of this study was to evaluate, over a wide The authors’ report demonstrates, across all phantom range of phantom sizes, CT number stability achieved sizes, the improvement in CT number stability achieved using two techniques for generating dual-energy computed with mono and mono+ relative to SE. tomography (DECT) virtual monoenergetic images. Results: Data exclusions were generally limited to cases when a SE or DE technique with a tube potential of less than 90 kV was used to scan a phantom larger than 30 cm. The 90/150Sn DE technique provided the most accurate water background over the large range of phantom sizes evaluated. Mono and mono+ provided equally improved CT number stability as a function of phantom size compared to SE; the average deviation in CT number was only 1.4% using 40 keV and 1.8% using 70 keV, while SE had an average deviation of 11.8%. https://pubmed.ncbi.nlm.nih.gov/26745944/ CT Dual Energy imaging in Radiation Oncology · Literature overview 25 Publications on CT Dual Energy in Radiation Therapy Rationale and design of a prospective study on the first integrated PET/dual-energy CT system for staging and Keywords: image-based radiation therapy planning of lung cancer • Biograph mCT • TwinBeam Dual Energy • Author: De Cecco C, Burchett P, van Assen M, Ravenel J, Rieter W, Schoepf J, Positron emission tomography Gordo L, Cooper S, Li H, Bradshaw M. • Contrast / iodine maps • Department of Radiology and Radiological Science, Target volume delineation Medical University of South Carolina, Charleston, USA. • Lung cancer (for complete affiliations see online article) • Tumor staging Date: Jul 2018 Purpose: Conclusion: The aim of this prospective study is to investigate the The results will add insights into the advantages of using diagnostic performance of integrated positron emission PET/DECT for lung cancer staging and for image-guided tomography (PET) /dual-energy computed tomography radiation therapy. (DECT) imaging in determining the thoracic nodal status of patients with small-cell lung cancer (SCLC) or non-small- cell lung cancer (NSCLC) and the resulting impact on target volume delineation for radiation therapy planning. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092731/ 26 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy CT Dual Energy imaging in Radiation Oncology · Literature overview 27 Publications on CT Dual Energy in Proton Therapy Dual-energy computed tomography to assess intra- and inter-patient tissue variability for proton treatment Keywords: planning of patients with brain tumor • SOMATOM Definition AS • Dual Spiral Dual Energy • Author: Wohlfahrt P, Möhler C, Troost EGC, Greilich S, Richter C. DirectSPR • Proton Therapy National Center for Radiation Research in Oncology, Technische Universität • Dresden, Dresden, Germany. (for complete affiliations see online article) Stopping Power Ratio / SPR • Monoenergetic / keV Date: Nov 2019 • Inter-patient variability • Primary brain tumor Purpose: Conclusion: Range prediction in particle therapy is associated with Accurate patient-specific DECT-based stopping-power an uncertainty originating from calculating the stopping- prediction allows for improved handling of tissue mixtures power ratio (SPR) based on x-ray computed tomography and can intrinsically incorporate most of the SPR variability (CT). Here, we assessed the intra- and inter-patient arising from tissue mixtures as well as inter-patient and variability of tissue properties in patients with primary intra-tissue variations. Since the state-of-the-art HLUT-even brain tumor using dual-energy CT (DECT) and quantified after cohort-specific optimization-cannot fully consider its influence on current SPR prediction. the broad tissue variability, patient-specific DECT-based stopping-power prediction is advisable in particle therapy. Results: An intra-patient ± inter-patient soft tissue diversity of 5.6% ± 0.7% in SPR (width of 95% confidence interval) was obtained including imaging- and model-related variations of up to 2.9%. This intra-patient SPR variability is associated with a mean absolute SPR deviation of 1.2% between the patient-specific DirectSPR approach and an optimal HLUT. Between adults and children younger than 6 years, age-related variations in bone composition resulted in a median SPR difference of approximately 5%. https://www.ncbi.nlm.nih.gov/pubmed/31271828 28 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Clinical feasibility of single-source dual-spiral 4D dual-energy CT for proton treatment planning within Keywords: the thoracic region • SOMATOM Definition AS • Dual Spiral Dual Energy • Author: Wohlfahrt P, Troost EGC, Hofmann C, Richter C, Jakobi A. syngo.via • Proton Therapy National Center for Radiation Research in Oncology, Technische Universität • Dresden, Dresden, Germany. (for complete affiliations see online article) Stopping Power Ratio / SPR • Monoenergetic / keV Date: Nov 2018 • Lung cancer Purpose: Conclusion: Single-source dual-spiral dual-energy computed tomo- The 79 keV pseudo-monoenergetic CT datasets can be graphy (DECT) provides additional patient information consistently obtained from dual-spiral 4D-DECT and are but is prone to motion between the 2 consecutively applicable for dose calculation. Patient-specific DECT-based acquired computed tomography (CT) scans. Here, the SPR prediction performed well and potentially reduces range clinical applicability of dual-spiral time-resolved DECT uncertainty in proton therapy of patients with lung cancer. (4D-DECT) for proton treatment planning within the thoracic region was evaluated. Results: Dual-spiral 4D-DECT scans without DIR showed a high geometric conformity, with an average NCC ± standard deviation of 98.7% ± 1.0% when including all patient voxels or 88.2% ± 7.8% when considering only lung. DIR improved the conformity, leading to an average NCC of 99.9% ± 0.1% and 99.6% ± 0.5%, respectively. PlanClin dose distributions on 140 kVp and 79 keV datasets were similar, with an average gamma passing rate of 99.9% (99.2%-100%). The worst-case evaluation still revealed high passing rates (99.3% on average, 92.4% as minimum). Clinically relevant mean range shifts of 2.2% ± 1.2% were determined between patient-specific DECT-based SPR prediction and clinical heuristic CT-number-to-SPR conversion. The intra- observer delineation variability was slightly reduced using additional DECT-derived datasets. https://www.ncbi.nlm.nih.gov/pubmed/30003998 CT Dual Energy imaging in Radiation Oncology · Literature overview 29 Publications on CT Dual Energy in Proton Therapy Clinical implementation of dual-energy CT for proton treatment planning on pseudo-monoenergetic CT scans Keywords: • SOMATOM Definition AS • Dual Spiral Dual Energy • Author: Wohlfahrt P, Möhler C, Hietschold V, Menkel S, Greilich S, Krause M, syngo.via Baumann M, Enghardt W, Richter C. • Proton Therapy • National Center for Radiation Research in Oncology, Technische Universität Stopping Power Ratio / SPR Dresden, Dresden, Germany. (for complete affiliations see online article) • Monoenergetic / keV • Beam hardening Date: Feb 2017 Purpose: Conclusion: To determine whether a standardized clinical application A standardized clinical use of MonoCT for treatment of dual-energy computed tomography (DECT) for proton planning is feasible, leads to improved image quality and treatment planning based on pseudomonoenergetic CT SPR prediction, extends diagnostic variety, and enables a scans (MonoCTs) is feasible and increases the precision of stepwise clinical implementation of DECT toward a physics- proton therapy in comparison with single-energy CT (SECT). based, patient-specific, nonheuristic SPR determination. Further reductions of CT-related uncertainties, as expected Results: from such SPR approaches, can be evaluated on the Dose distributions planned on SECT and MonoCT datasets resulting DECT patient database. revealed mean range deviations of 0.3 mm, γ passing rates (1%, 1 mm) greater than 99.9%, and no clinically relevant changes in dose-volume histograms. However, image noise and CT-related uncertainties could be reduced by MonoCT compared with SECT, which resulted in a slightly decreased dependence of SPR prediction on beam hardening. Consequently, DECT was clinically implemented at the University Proton Therapy Dresden in 2015. Until October 2016, 150 patients were treated based on MonoCTs, and more than 950 DECT scans of 351 patients were acquired during radiation therapy. https://www.ncbi.nlm.nih.gov/pubmed/28068248 30 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Dual-energy CT based proton range prediction in head and pelvic tumor patients Keywords: • SOMATOM Definition AS • Dual Spiral Dual Energy • Author: Wohlfahrt P, Möhler C, Stützer K, Greilich S, Richter C. Proton Therapy • Stopping Power Ratio / SPR National Center for Radiation Research in Oncology, Technische Universität prediction Dresden, Dresden, Germany. (for complete affiliations see online article) • RhoSigma Date: Dec 2017 • Head tumor • Prostate cancer Purpose: Conclusion: To reduce range uncertainty in particle therapy, an The magnitude of patient-specific range deviations accurate computation of stopping-power ratios (SPRs) between HLUT and the more accurate DECT-based SPR based on computed tomography (CT) is crucial. Here, we prediction is clinically relevant. A clinical application of assess range differences between the state-of-the-art the latter seems feasible as demonstrated in this study CT-number-to-SPR conversion using a generic Hounsfield using medically approved systems from CT acquisition to look-up table (HLUT) and a direct patient-specific SPR treatment planning. prediction (RhoSigma) based on dual-energy CT (DECT) in 100 proton treatment fields. Results: Absolute (relative) mean water-equivalent range shifts of 1.1mm (1.2%) and 4.1mm (1.7%) were observed in the head-tumor and prostate-cancer cohort, respectively. Due to the case dependency of a generic HLUT, range deviations within treatment fields strongly depend on the tissues traversed leading to a larger variation within one patient than between patients https://www.ncbi.nlm.nih.gov/pubmed/29050953 CT Dual Energy imaging in Radiation Oncology · Literature overview 31 Publications on CT Dual Energy in Proton Therapy Refinement of the Hounsfield look‐up table by retrospective application of patient-specific direct proton stopping-power Keywords: prediction from dual-energy CT • SOMATOM Definition AS Open • Dual Spiral Dual Energy • Author: Wohlfahrt P, Möhler C, Enghardt W, Krause M, Kunath D, Menkel S, Proton Therapy Troost E, Greilich S, Richter C. • Stopping Power Ratio / SPR • National Center for Radiation Research in Oncology, Hounsfield look-up table Technische Universität Dresden, Germany. (for complete affiliations see online article) Date: Apr 2020 Purpose: Conclusion: Proton treatment planning relies on an accurate The incorporation of patient-specific correlations determination of stopping-power ratio (SPR) from x-ray between CT number and SPR, derived from a retrospective computed tomography (CT). A refinement of the heuristic application of DirectSPR to a broad patient cohort, CT-based SPR prediction using a state-of-the-art improves the SPR accuracy of the current state-of-the-art Hounsfield look-up table (HLUT) is proposed, which HLUT approach. The DirectSPR-based adapted HLUT has incorporates patient SPR information obtained from dual- been clinically implemented at the University Proton energy CT (DECT) in a retrospective patient-cohort analysis. Therapy Dresden (Dresden, Germany) in 2017. This already facilitates the benefits of an improved DECT-based tissue Results: differentiation within clinical routine without changing The application of the DirectSPR-based adapted HLUT the general approach for range prediction (HLUT), and instead of the nonadapted HLUT reduced the systematic represents a further step toward full integration of the proton range differences from 1.2% (1.1 mm) to -0.1% DECT-based DirectSPR method for treatment planning (0.0 mm) for brain-tumor patients, 1.7% (4.1 mm) to in proton therapy. 0.2% (0.5 mm) for prostate-cancer patients, and 2.0% (2.9 mm) to -0.1% (0.0 mm) for NSCLC patients. Due to the large intra- and inter-patient tissue variability, range differences to DirectSPR larger than 1% remained for the adapted HLUT. https://pubmed.ncbi.nlm.nih.gov/32037543/ 32 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Evaluating clinical stopping power estimation from a radiotherapy dual energy CT scanner Keywords: • SOMATOM Definition AS Open • syngo.via • Author: Almeida I, Landry G, Dedes G. Dual Spiral Dual Energy • Proton Therapy Department of Radiation Oncology (MAASTRO), • Maastricht University Medical Centre, the Netherlands. Stopping Power Ratio / SPR (for complete affiliations see online article) Date: Jan 2017 Abstract: The use of dual energy computed tomography (DECT) is values calculated using syngo.via (Hudobivnik) against increasingly considered in particle therapy (PT) to reduce reference values were 1.0% (0.7%). This difference the range of uncertainties attributed to the conversion of excludes the lung inserts as the syngo. via method does X-ray linear attenuation coefficients into relative stopping not provide that Zeff values for CT numbers < -500 HU. power (RSP). DECT scanners equipped with clinically An analysis of the head phantom showed overall a good available image conversion software can now be found agreement with all RSP differences within 1% between in PT centers. In this work, RSP calculated on the basis of the syngo.via and Hudobivnik methods. The use of clinical DECT scanner software (syngo.via) was compared clinically available syngo.via provides equivalent accuracy to a validated published procedure (Hudobivnik) for as a validated RSP calculation method. calibration and pediatric head phantoms. Based on material inserts, the average difference between RSP https://www.researchgate.net/publication/320897405_Evaluating_Clinical_ Stopping_Power_Estimation_from_a_Radiotherapy_Dual_Energy_CT_Scanner CT Dual Energy imaging in Radiation Oncology · Literature overview 33 Publications on CT Dual Energy in Proton Therapy Determination of proton stopping power ratio with dual- energy CT in 3D-printed tissue/air cavity surrogates Keywords: • SOMATOM Definition Edge • Twin Beam Dual Energy • Author: Polf JC, Mille MM, Mossahebi S, Chen H, Maggi P, Chen-Mayer H. Stopping Power Ratio / SPR • Proton Therapy Department of Radiation Oncology, University of Maryland School of • Medicine, Baltimore, USA. (for complete affiliations see online article) 3D printing Date: Jul 2019 Purpose: Conclusion: To study the accuracy with which proton stopping power Overall, the DECT-based SPR-CT was within 3% of SPR-TH ratio (SPR) can be determined with dual-energy computed and SPR-DM in the high-density gradient regions of tomography (DECT) for small structures and bone-tissue-air the 3D-printed plugs for septa greater than ~ 3mm interfaces like those found in the head or in the neck. in thickness. Results: The SPR-CT for PLA agreed with SPR-DM for tsepta ≥ 3 mm (for CT slice thicknesses of 0.5, 1.0, and 3.0 mm). The density of PLA was found to decrease with thickness when tsepta < 3 mm. As tsepta (and density) decreased, the SPR-CT values also decreased, in good agreement with SPR-DM and SPR-TH. https://www.ncbi.nlm.nih.gov/pubmed/31081542 34 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Monte Carlo proton dose calculations using a radiotherapy specific dual-energy CT scanner for tissue segmentation Keywords: and range assessment • SOMATOM Definition Edge • SOMATOM Confidence RT Pro • Author: Almeida IP, Schyns L, Vaniqui A, van der Heyden B, Dedes G, Resch A, SOMATOM Force Kamp F, Zindler Jaap, Parodi K, Landry G, Verhaegen F. • Dual Spiral Dual Energy • Department of Radiation Oncology (MAASTRO), Twin Beam Dual Energy Maastricht University Medical Centre, the Netherlands. • Dual Source Dual Energy (for complete affiliations see online article) • Proton Therapy • Proton dose calculations Date: May 2018 • Tissue segmentation • Proton range Abstract: Proton beam ranges derived from dual-energy computed different image-based simulations were assessed. tomography (DECT) images from a dual-spiral For phantoms, the DECT method yielded overall better radiotherapy (RT)-specific CT scanner were assessed material segmentation with >86% of the voxel correctly using Monte Carlo (MC) dose calculations. Images from assigned for the dual-spiral and dual-source scanners, a dual-source and a twin-beam DECT scanner were also but only 64% for a twin-beam scanner. For the calibration used to establish a comparison to the RT-specific scanner. phantom, the dual-spiral scanner yielded range errors Proton ranges extracted from conventional single-energy below 1.2 mm (0.6% of range), like the errors yielded CT (SECT) were additionally performed to benchmark by the dual-source scanner (<1.1 mm, <0.5%). With the against literature values. Using two phantoms, a DECT validation phantom, the dual-spiral scanner yielded errors methodology was tested as input for Geant4 MC proton below 0.8 mm (0.9%), whereas SECT yielded errors up dose calculations. Proton ranges were calculated for to 1.6 mm (2%). For the patient case, where the absolute different mono-energetic proton beams irradiating both truth was missing, proton range differences between phantoms; the results were compared to the ground DECT and SECT were on average in -1.2 ± 1.2 mm truth based on the phantom compositions. The same (-0.5% ± 0.5%). MC dose calculations were successfully methodology was applied in a head-and-neck cancer performed on DECT images, where the dual-spiral patient using both SECT and dual-spiral DECT scans from scanner resulted in media segmentation and range the RT-specific scanner. A pencil-beam-scanning plan accuracy as good as the dual-source CT. In the patient, was designed, which was subsequently optimized by MC the various methods showed relevant range differences. dose calculations, and differences in proton range for the https://pubmed.ncbi.nlm.nih.gov/29616662/ CT Dual Energy imaging in Radiation Oncology · Literature overview 35 Publications on CT Dual Energy in Proton Therapy Influence of intravenous contrast agent on dose calculation in proton therapy using dual energy CT Keywords: • SOMATOM Definition Edge • TwinBeam Dual Energy • Author: Lalonde A, Xie Y, Burgdorf B, O’Reilly S, Ingram W, Yin L, You W, Proton Therapy Dong L, Bouchard H, Teo B. • Stopping Power Ratio / SPR • Département de Physique, Université de Montréal, Montréal, Canada. Intravenous contrast agent (for complete affiliations see online article) • Dose calculation • Virtual non-contrast / VNC Date: Jun 2019 Abstract: The purpose of this study is to evaluate the effect of an is evaluated for one liver and one head and neck patient. intravenous (IV) contrast agent on proton therapy dose Using simulated data, DECT is shown to be less sensitive calculation using dual-energy computed tomography to the presence of IV contrast than SECT, although the (DECT). Two DECT methods are considered. The first one, performance of the ρe -Zmed method is sensitive to the level ρe -Zmed, attempts to accurately predict the proton stopping of beam hardening considered. For different concentrations powers relative to water (SPR) of contrast enhanced (CE) of IV contrast diluted in water, experimental MLIC DECT images, while the second generates a virtual measurement of SPR agrees with DECT predictions within non-contrast (VNC) volume that can be processed as a 3% while SECT introduce errors above 20%. This error native non-contrast (NC) one. Both methods are compared in the SPR value results in a range error of up to 3.2 mm against single-energy computed tomography (SECT). (2.6%) for proton beams calculated on SECT CE patient The accuracy of SPR predicted for different concentrations images. The error is reduced below 1mm using DECT with of IV contrast diluted in water is first evaluated using the ρe -Zmed and VNC methods. Globally, it is observed that simulated data. Results then are validated in an the influence of IV contrast on proton therapy dose experimental set-up comparing SPR predictions for both calculation is mitigated using DECT over SECT. In patient NC and CE images to measurements made with a multi- anatomies, the VNC approach provides the best agreement layer ionisation chamber (MLIC). Finally, the impact of IV with the reference dose distribution. contrast on dose calculation using both SECT and DECT https://pubmed.ncbi.nlm.nih.gov/31044743/ 36 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy A simulation study on proton computed tomography (CT) stopping power accuracy using dual energy CT scans Keywords: as benchmark • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Hansen DC, Seco J, Sørensen TS, Petersen JB, Wildberger JE, Proton Therapy Verhaegen F, Landry G. • Stopping Power Ratio / SPR Department of Oncology , Aarhus University Hospital , Aarhus , Denmark. (for complete affiliations see online article) Date: Jul 2015 Background: Conclusion: Accurate stopping power estimation is crucial for treatment Better stopping power estimates could significantly planning in proton therapy, and the uncertainties in reduce the range errors in proton therapy, but requires stopping power are currently the largest contributor to a large improvement in current methods which may be the employed dose margins. Dual energy x-ray computed achievable with proton CT. tomography (CT) (clinically available) and proton CT (in development) have both been proposed as methods for obtaining patient stopping power maps. The purpose of this work was to assess the accuracy of proton CT using dual energy CT scans of phantoms to establish reference accuracy levels. Results: Proton CT gave slightly better stopping power estimates than the dual energy CT method, with root mean square errors of 0.2% and 0.5% (for each phantom) compared to 0.5% and 0.9%. Single energy CT root mean square errors were 2.7% and 1.6%. Maximal errors for proton, dual energy and single energy CT were 0.51%, 1.7% and 7.4%, respectively. https://www.ncbi.nlm.nih.gov/pubmed/26219959 CT Dual Energy imaging in Radiation Oncology · Literature overview 37 Publications on CT Dual Energy in Proton Therapy Experimental validation of two dual-energy CT methods for proton therapy using heterogeneous tissue samples Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Bär E, Lalonde A, Zhang R, Jee KW, Yang K, Sharp G, Liu B, Royle G, Proton Therapy Bouchard H, Lu HM. • Stopping Power Ratio / SPR Prediction Acoustics and Ionising Radiation Team, National Physical Laboratory, Teddington, United Kingdom. (for complete affiliations see online article) Date: Jan 2018 Purpose: Conclusion: The purpose of this work is to evaluate the performance The present work uses experimental measurements in of dual-energy CT (DECT) for determining proton stopping a realistic clinical environment to show potential benefits power ratios (SPRs) in an experimental environment and of DECT for proton therapy treatment planning. Our results to demonstrate its potential advantages over conventional show clear improvements over SECT in tissue-equivalent single-energy CT (SECT) in clinical conditions. plastic materials and animal tissues. Further work towards using Monte Carlo simulations for treatment planning Results: with DECT data and a more detailed investigation of For homogeneous tissue-equivalent plastic materials, the uncertainties on I-value and limitations on the Bragg results with DECT are consistent with experimental additivity rule could potentially further enhance the measurements and show a systematic reduction of SPR benefits of this imaging technology for proton therapy. uncertainty compared to SECT, with root-mean-square errors of 1.59% versus 0.61% for SECT and DECT, respectively. Measurements with heterogeneous animal samples show a clear reduction of the bias on range predictions in the presence of bones, with -0.88% for SECT versus -0.58% and -0.14% for both DECT methods. An uncertainty budget allows isolating the effect of CT number conversion to SPR and predicts improvements by DECT over SECT consistently with theoretical predictions, with 0.34% and 0.31% for soft tissues and bones in the experimental setup compared to 0.34% and 1.14% with the theoretical method. https://www.ncbi.nlm.nih.gov/pubmed/29134674 38 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy The impact of dual- and multi-energy CT on proton pencil beam range uncertainties: A Monte Carlo study Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Lalonde A, Simard M, Remy C, Bär E, Bouchard H. Proton Therapy • Mass Density Département de Physique, Université de Montréal, Pavillon Roger-Gaudry, , • Montréal, Canada. (for complete affiliations see online article) Stopping Power Ratio / SPR Date: Sept 2018 Abstract: The purpose of this work is to evaluate the impact of Percentage depth doses curves (PDD) are compared to single-, dual- and multi-energy CT (SECT, DECT and MECT) ground truth in order to determine the accuracy of range on proton range uncertainties in a patient like geometry prediction of each imaging modality. For the idealistic and a full Monte Carlo environment. A virtual patient is images of case A, MECT and DECT slightly outperforms generated from a real patient pelvis CT scan, where SECT. Root mean square (RMS) errors or 0.78 mm, known mass densities and elemental compositions are 0.49mm and 0.42mm on R 80 mm, are observed for SECT, overwritten in each voxel. Simulated CT images for SECT, DECT and MECT respectively. In case B, PDD calculated DECT and MECT are generated for two limiting cases: in the MECT derived Monte Carlo inputs generally shows (1) theoretical and idealistic CT numbers only affected the best agreement with ground truth in both shape and by Gaussian noise (case A, the best scenario) and position, with RMS errors of 2.03 mm, 1.38 mm and (2) reconstructed polyenergetic sinograms containing 0.86 mm for SECT, DECT and MECT respectively. Overall, beam hardening, projection-based Poisson noise, and the Bayesian eigentissue decomposition used with DECT reconstruction artifacts (case B, the worst scenario). systematically predicts proton ranges more accurately Conversion of the simulated SECT images into Monte Carlo than the gold standard SECT-based approach. When inputs is done following the stoichiometric calibration CT numbers are severely affected by imaging artifacts, method. For DECT and MECT, the Bayesian eigentissue MECT with four energy bins becomes more reliable than decomposition method of Lalonde (2017 Med. Phys. 44 both DECT and SECT. 5293-302) is used. Pencil beams from seven different angles around the virtual patient are simulated using TOPAS to assess the performance of each method. https://www.ncbi.nlm.nih.gov/pubmed/30183681 CT Dual Energy imaging in Radiation Oncology · Literature overview 39 Publications on CT Dual Energy in Proton Therapy A stoichiometric calibration method for dual energy computed tomography Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Bourque AE, Carrier JF, Bouchard H. Stopping Power Ratio / SPR • Proton Therapy Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Canada. • (for complete affiliations see online article) Monoenergetic / keV • Electron Density Date: Apr 2014 Abstract: The accuracy of radiotherapy dose calculation relies crucially A fit of mean excitation energy (I-value) data as a function on patient composition data. The computed tomography of EAN is provided in order to determine the ion stopping (CT) calibration methods based on the stoichiometric power of human tissues from ED-EAN measurements. calibration of Schneider et al (1996 Phys. Med. Biol. 41 Analysis of the calibration phantom measurements with 111-24) are the most reliable to determine electron the Siemens SOMATOM Definition Flash dual source CT density (ED) with commercial single energy CT scanners. scanner shows that the present formalism yields mean Along with the recent developments in dual energy CT absolute errors of (0.3 ± 0.4)% and (1.6 ± 2.0)% on ED and (DECT) commercial scanners, several methods were EAN, respectively. For ion therapy, the mean absolute published to determine ED and the effective atomic errors for calibrated I-values and proton stopping powers number (EAN) for polyenergetic beams without the need (216 MeV) are (4.1 ± 2.7)% and (0.5 ± 0.4)%, respectively. for CT calibration curves. This paper intends to show that In all clinical situations studied, the uncertainties in ion with a rigorous definition of the EAN, the stoichiometric ranges in water for therapeutic energies are found to be calibration method can be successfully adapted to DECT less than 1.3 mm, 0.7 mm and 0.5 mm for protons, helium with significant accuracy improvements with respect to and carbon ions respectively, using a generic reconstruction the literature without the need for spectrum measurements algorithm (filtered back projection). With a more or empirical beam hardening corrections. Using a theo- advanced method (sinogram affirmed iterative technique), retical framework of ICRP human tissue compositions and the values become 1.0 mm, 0.5 mm and 0.4 mm for the XCOM photon cross sections database, the revised protons, helium and carbon ions, respectively. These stoichiometric calibration method yields Hounsfield unit results allow one to conclude that the present adaptation (HU) predictions within less than ±1.3 HU of the theoretical of the stoichiometric calibration yields a highly accurate HU calculated from XCOM data averaged over the spectra method for characterizing tissue with DECT for ion beam used (e.g., 80 kVp, 100 kVp, 140 kVp and 140/Sn kVp). therapy and potentially for photon beam therapy. https://www.ncbi.nlm.nih.gov/pubmed/24694786 40 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy The potential of dual-energy CT to reduce proton beam range uncertainties Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Bär E, Lalonde A, Royle G, Lu H, Bouchard H. Proton Therapy • Stopping Power Ratio / SPR Acoustics and Ionising Radiation Team, National Physical Laboratory, • Teddington, UK. (for complete affiliations see online article) Range uncertainties • Tissue characterization Date: Apr 2017 Purpose: Results: Dual-energy CT (DECT) promises improvements in Range error estimations demonstrate that DECT has the estimating stopping power ratios (SPRs) for proton therapy potential of reducing proton beam range uncertainties treatment planning. Although several comparable by 0.4% in soft tissues using low noise levels of 12 and mathematical formalisms have been proposed in 8 HU in DECT, corresponding to 7 HU in SECT. For range literature, the optimal techniques to characterize human uncertainties caused by the transport of protons through tissue SPRs with DECT in a clinical environment are not bones, the reduction in range uncertainties for the same fully established. The aim of this work is to compare levels of noise is found to be up to 0.6 to 1.1 mm for the most robust DECT methods against conventional bone thicknesses ranging from 1 to 5 cm, respectively. single-energy CT (SECT) in conditions reproducing We also show that for double the amount noise, i.e., a clinical environment, where CT artifacts and noise play 14 HU in SECT and 24 and 16 HU for DECT, the advantages a major role on the accuracy of these techniques. of DECT in soft tissues are lost over SECT. In bones however, the reduction in range uncertainties is found to be between 0.5 and 0.9 mm for bone thicknesses ranging from 1 to 5 cm, respectively. Conclusion: DECT has a clear potential to improve proton beam range predictions over SECT in proton therapy. However, in the current state high levels of noise remain problematic for DECT characterization methods and do not allow getting the full benefits of this technology. Future work should focus on adapting DECT methods to noise and investigate methods based on raw-data to reduce CT artifacts. https://pubmed.ncbi.nlm.nih.gov/28295434/ CT Dual Energy imaging in Radiation Oncology · Literature overview 41 Publications on CT Dual Energy in Proton Therapy Experimental verification of ion stopping power prediction from dual energy CT data in tissue surrogates Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Hünemohr N, Krauss B, Tremmel C, Ackermann B, Jäkel O, Greilich S. Proton Therapy • Stopping Power Ratio / SPR Division of Medical Physics in Radiation Oncology, • German Cancer Research Center, Germany. Tissue surrogates (for complete affiliations see online article) • Electron density Date: Dec 2014 Abstract: We present an experimental verification of stopping- For the tissue surrogates the presented DECT approach power-ratio (SPR) prediction from dual energy CT (DECT) was found to predict the experimental values within with potential use for dose planning in proton and ion 0.6%, for aluminum and titanium within an accuracy of therapy. The approach is based on DECT images 1.7% and 9.4% (from 16-bit reconstructed DECT images). converted to electron density relative to water ρe /ρe,w and effective atomic number Zeff. To establish a parameterization of the I-value by Zeff, 71 tabulated tissue compositions were used. For the experimental assessment of the method we scanned 20 materials (tissue surrogates, polymers, aluminum, titanium) at 80/140Sn kVp and 100/140Sn kVp (Sn: additional tin filtration) and computed the ρe /ρe,w and Zeff with a purely image based algorithm. Thereby, we found that ρe /ρe,w (Zeff) could be determined with an accuracy of 0.4% (1.7%) for the tissue surrogates with known elemental compositions. SPRs were predicted from DECT images for all 20 materials using the presented approach and were compared to measured water-equivalent path lengths (closely related to SPR). https://pubmed.ncbi.nlm.nih.gov/24334601/ 42 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Tissue decomposition from dual energy CT data for MC based dose calculation in particle therapy Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Hünemohr N, Paganetti H, Greilich S, Jäkel O, Seco J. Proton Therapy • Stopping Power Ratio / SPR Medical Physics in Radiation Oncology, German Cancer Research Center, • Germany. (for complete affiliations see online article) Stoichiometric calibration • Monte Carlo based Date: Jun 2014 dose planning • Tissue decomposition • Range uncertainty Purpose: The authors describe a novel method of predicting mass Dose studies showed that most of the 12 selected tissues density and elemental mass fractions of tissues from would profit significantly (up to 2.2%) from DECT dual energy CT (DECT) data for Monte Carlo (MC) based material decomposition with no noise present. The ρe dose planning. associated with an absolute noise of ±0.01 and Zeff associated with an absolute noise of ±0.2 resulted in ±10% Results: standard variation in the carbon and oxygen mass Mean deviations to ground truth in mass density fraction prediction. predictions could be reduced for soft tissue from (0.5±0.6)% (SECT) to (0.2±0.2)% with the DECT method. Conclusion: Maximum SPR deviations could be reduced significantly Accurate stopping power prediction is mainly determined for soft tissue from 3.1% (SECT) to 0.7% (DECT) and for by the correct mass density prediction. Theoretical bone tissue from 0.8% to 0.1%. Mean I-value deviations improvements in range predictions with DECT data in the could be reduced for soft tissue from (1.1±1.4%, SECT) order of 0.1%–2.1% were observed. Further work is to (0.4±0.3%) with the presented method. Predictions of needed to quantify the potential improvements from elemental composition were improved for every element. DECT compared to SECT in measured image data Mean and maximum deviations from ground truth of all associated with artifacts and noise. elemental mass fractions could be reduced by at least a half with DECT compared to SECT (except soft tissue hydrogen and nitrogen where the reduction was slightly smaller). The carbon and oxygen mass fraction predictions profit especially from the DECT information. https://pubmed.ncbi.nlm.nih.gov/24877809/ CT Dual Energy imaging in Radiation Oncology · Literature overview 43 Publications on CT Dual Energy in Proton Therapy Technical note: improving proton stopping power ratio determination for a deformable silicone-based 3D Keywords: dosimeter using dual energy CT • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Taasti VT, Høye EM, Hansen DC, Muren L, Thygesen J, Skyt P, Balling P, Proton Therapy Bassler N, Grau C, Mierzwinska G, Rydygier M, Swakon J, Olko P, Petersen J. • Stopping Power Ratio / SPR • Department of Medical Physics, Aarhus University/Aarhus University Hospital, Stoichiometric method Denmark. (for complete affiliations see online article) • Beam delivery verification Date: Jun 2016 Purpose: Conclusion: The aim of this study was to investigate whether The SPR of the dosimeter was overestimated by 13% the stopping power ratio (SPR) of a deformable, silicone- using the stoichiometric method and by 3% when using based 3D dosimeter could be determined more accurately DECT. If the stoichiometric method should be applied using dual energy (DE) CT compared to using conventional for the dosimeter, the HU of the dosimeter must be methods based on single energy (SE) CT. The use of SECT manually changed in the treatment planning system combined with the stoichiometric calibration method in order to give a correct SPR estimate. Using a wrong was therefore compared to DECT-based determination. SPR value will cause differences between the calculated and the delivered treatment plans. Results: The SPR determined from SECT and the stoichiometric method was 1.10, compared to 1.01 with both DECT calibration methods. The measured SPR for the dosimeter material was 0.97. https://pubmed.ncbi.nlm.nih.gov/27277025/ 44 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Experimental verification of stopping-power prediction from single- and dual-energy computed tomography Keywords: in biological tissues • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Möhler C, Russ T, Wohlfahrt P, Elter A, Runz A, Richter C, Greilich S. Proton Therapy • Stopping Power Ratio / SPR German Cancer Research Center (DKFZ), Heidelberg, Germany. • (for complete affiliations see online article) Range verification Date: Jan 2018 Abstract: An experimental setup for consecutive measurement approach, SPR was predicted for all tissues and then of ion and x-ray absorption in tissue or other materials is compared to the measured reference. With the SECT introduced. With this setup using a 3D-printed sample approach, the SPRs of all tissues were predicted with container, the reference stopping-power ratio (SPR) of a mean error of (−0.84 ± 0.12)% and a mean absolute materials can be measured with an uncertainty of below error of (1.27 ± 0.12)%. In contrast, the DECT-based SPR 0.1%. A total of 65 porcine and bovine tissue samples predictions were overall consistent with the measured were prepared for measurement, comprising five samples reference with a mean error of (−0.02 ± 0.15)% and each of 13 tissue types representing about 80% of the total a mean absolute error of (0.10 ± 0.15)%. Thus, in this body mass (three different muscle and fatty tissues, study, the potential of DECT to decrease range uncertainty liver, kidney, brain, heart, blood, lung and bone). Using could be confirmed in biological tissue. a standard stoichiometric calibration for single-energy CT (SECT) as well as a state-of-the-art dual-energy CT (DECT) https://pubmed.ncbi.nlm.nih.gov/29239855/ CT Dual Energy imaging in Radiation Oncology · Literature overview 45 Publications on CT Dual Energy in Proton Therapy Comparison of single and dual energy CT for stopping power determination in proton therapy of head and neck cancer Keywords: • SOMATOM Definition Flash • Dual Source Dual Energy • Author: Taasti V, Muren L, Jensen K, Tietze A. Grau C, Hansen D Proton Therapy • Stopping Power Ratio / SPR Published by Elsevier B.V. on behalf of European Society of • Radiotherapy & Oncology. Head and neck cancer Date: Jun 2018 Purpose: Conclusion: Patients with head and neck (HN) cancer may benefit Clinically relevant WEPL and SPR differences were found from proton therapy due to the potential for sparing of between DECT and SECT, which could imply that the normal tissue. For planning of proton therapy, dual- accuracy of treatment planning for proton therapy would energy CT (DECT) has been shown to provide superior benefit from DECT-based SPR estimation. stopping power ratio (SPR) determination in phantom materials and organic tissue samples, compared to single-energy CT (SECT). However, the benefit of DECT in HN cancer patients has not yet been investigated. This study therefore compared DECT- and SECT-based SPR estimation for HN cancer patients. Results: A median WEPL difference of 1.9 mm (1.5%) was found across the eight patients. Statistically significant SPR differences were seen for the ROIs in the brain and eyes, with the SPR estimates based on DECT overall lower than for SECT. https://www.phiro.science/article/S2405631617300842/abstract 46 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Evaluation of stopping-power prediction by dual- and single-energy computed tomography in an anthropo- Keywords: morphic ground-truth phantom • SOMATOM Force • SOMATOM Definition AS • Author: Wohlfahrt P, Möhler C, Richter C, Greilich S. Dual Source Dual Energy • Dual Spiral Dual Energy National Center for Radiation Research in Oncology, Technische Universität • Dresden, Dresden, Germany. (for complete affiliations see online article) Proton Therapy • DirectSPR Date: Jan 2018 Purpose: Conclusion: To determine the accuracy of particle range prediction DirectSPR predictions proved to be more robust, with for proton and heavier ion radiation therapy based on high accuracy in particular for larger volumes. In contrast, dual-energy computed tomography (DECT) in a realistic HLUT approaches exhibited a fortuitous component. inhomogeneous geometry and to compare it with The evaluation of accuracy in a realistic phantom with the state-of-the-art clinical approach. validated ground-truth SPR represents a crucial step toward possible clinical application of DECT-based SPR Results: prediction methods. The established reference SPR map was successfully validated for the discrimination of SPR and range differences well below 0.3% and 1 mm, respectively, even in complex inhomogeneous settings. For the phantom materials of larger volume (mainly brain, soft tissue), the investigated methods were overall able to predict SPR within 1% median deviation. The DirectSPR methods generally performed better than the HLUT approaches. For smaller phantom parts (such as cortical bone, air cavities), all methods were affected by image smoothing, leading to considerable SPR under- or overestimation. This effect was superimposed on the general SPR prediction accuracy in the exemplary treatment plan. https://www.ncbi.nlm.nih.gov/pubmed/29079119 CT Dual Energy imaging in Radiation Oncology · Literature overview 47 Publications on CT Dual Energy in Proton Therapy A comparison of relative proton stopping power measurements across patient size using dual- and Keywords: single-energy CT • SOMATOM Force • Dual Source Dual Energy • Author: Michalak G, Taasti V, Krauss B, Deisher A, Halaweish A, McCollough C. Proton Therapy • Stopping Power Ratio / SPR Department of Radiology , Mayo Clinic , Rochester , MN , USA. • (for complete affiliations see online article) Rho-Z • Electron Density Date: Nov 2017 Purpose: Conclusion: To evaluate the accuracy and precision across phantom We demonstrate the superior ability of DECT to mitigate size of a dual-energy computed tomography (DECT) systematic bias in bones and liver and estimate SPR in technique used to calculate relative proton stopping a silicone breast implant. power (SPR) in tissue-simulating materials and a silicone implant relative to conventional single-energy CT (SECT). Results: Both DECT and SECT SPR data resulted in good agreement with the reference values. Percent error was ±3% for both DECT and SECT in all materials except lung and dense bone. The coefficient of variation (CV) across materials and phantom sizes was 1.12% for SECT and 0.96% for DECT. Material-specific regression and graphical analysis did not reveal size dependence for either technique but did show reduced systematic bias with DECT for dense bone and liver. Mean percent error in SPR for the implant was reduced from 11.46% for SECT to 0.49% for DECT. https://www.ncbi.nlm.nih.gov/pubmed/28885130 48 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Experimental comparison of proton CT and dual energy X–ray CT for relative stopping power estimation Keywords: in proton therapy • SOMATOM Force • Dual Source Dual Energy • Author: Dedes G, Dickmann J, Niepel K, Wesp P, Johnson R, Pankuch M, Proton Therapy Bashkirov V, Rit S, Volz L, Schulte R, Landry G, Parodi K. • Stopping Power Ratio / SPR • Department of Medical Physics, Ludwig-Maximilians-Universität München, Proton CT Monte Carlo Germany. (for complete affiliations see online article) simulations Date: Jun 2019 Abstract: Proton computed tomography (pCT) has been proposed degraded MAPE. MAPE was 0.55% for pCT and 0.67% as an alternative to x-ray computed tomography (CT) for for DECT. The realistic MC simulation agreed well with acquiring relative to water stopping power (RSP) maps pCT measurements (MAPE = 0.69%). Both simulation and used for proton treatment planning dose calculations. experimental results showed ring artifacts in pCT images In parallel, it has been shown that dual energy x-ray CT which degraded the MAPE compared to an ideal pCT (DECT) improves RSP accuracy when compared to simulation (MAPE = 0.17%). Using the realistic conventional single energy x-ray CT. This study aimed at simulation, we could identify sources of artifacts, which directly comparing the RSP accuracy of both modalities are attributed to the interfaces in the five-stage plastic using phantoms scanned at an advanced prototype scintillator energy detector and calibration curve pCT scanner and a state-of-the-art DECT scanner. interpolation regions. Secondary artifacts stemming Two phantoms containing 13 tissue-mimicking inserts from the proton tracker geometry were also identified. of known RSP were scanned at the pCT phase II prototype The pCT prototype scanner outperformed a state-of- and a latest generation dual-source DECT scanner the-art DECT scanner in terms of RSP accuracy (MAPE) (Siemens SOMATOM Definition FORCE). RSP accuracy was for plastic tissue mimicking inserts. Since artifacts tended compared by mean absolute percent error (MAPE) over to concentrate in the inserts, their mitigation may lead to all inserts. A highly realistic Monte Carlo (MC) simulation further improvements in the reported pCT accuracy. was used to gain insight on pCT image artifacts which https://pubmed.ncbi.nlm.nih.gov/31220814/ CT Dual Energy imaging in Radiation Oncology · Literature overview 49 Publications on CT Dual Energy in Proton Therapy Comparison of proton therapy treatment planning for head tumors with a pencil beam algorithm on dual Keywords: and single energy CT images • SOMATOM Force • Dual Source Dual Energy • Author: Hudobivnik N, Schwarz F, Johnson T, Agolli L, Dedes G, Tessonnier T, Proton Therapy Verhaegen F, Thieke C, Belka C, Sommer W, Parodi K, Landry G. • Stopping Power Ratio / SPR • Department of Medical Physics, Ludwig-Maximilians-University, Germany. Head tumors (for complete affiliations see online article) Date: Jan 2016 Purpose: Results: Dual energy CT (DECT) has recently been proposed as an SPR root mean square errors (RMSEs) for the inserts improvement over single energy CT (SECT) for stopping of the Gammex phantom were 1.9%, 1.8%, and 1.2% power ratio (SPR) estimation for proton therapy for SECT phantom calibration (SECTphantom), SECT treatment planning (TP), thereby potentially reducing stoichiometric calibration (SECTstoichiometric), and DECT range uncertainties. Published literature investigated calibration, respectively. For the CIRS phantom, these phantoms. This study aims at performing proton therapy were 3.6%, 1.6%, and 1.0%. When investigating patient TP on SECT and DECT head images of the same patients anatomy, group median range differences of up to -1.4% and at evaluating whether the reported improved DECT were observed for head cases when comparing SPR accuracy translates into clinically relevant range SECTstoichiometric with DECT. For this calibration the shifts in clinical head treatment scenarios. 25th and 75th percentiles varied from -2% to 0% across the five patients. The group median was found to be limited to 0.5% when using SECTphantom and the 25th and 75th percentiles varied from -1% to 2%. Conclusion: Proton therapy TP using a pencil beam algorithm and DECT images was performed for the first time. Given that the DECT accuracy as evaluated by two phantoms was 1.2% and 1.0% RMSE, it is questionable whether the range differences reported here are significant. https://pubmed.ncbi.nlm.nih.gov/26745942/ 50 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Systematic analysis of the impact of imaging noise on dual- energy CT-based proton stopping-power-ratio estimation Keywords: • SOMATOM Force • Dual Source Dual Energy • Author: Lee HHC, Li B, Duan X, Zhou L, Jia X, Yang M Effective atomic number • Electron density ratio Department of Radiation Oncology, • University of Texas Southwestern Medical Center, Dallas, USA. (for complete Proton Therapy affiliations see online article) • Stopping Power Ratio / SPR • Impact of noise Date: May 2019 Purpose: Dual-energy CT (DECT) has been shown to have a great Overall, the range uncertainty (95th percentile) caused potential in reducing the uncertainty in proton stopping by noise was within 1.2% and 1.0% for soft and bone power ratio (SPR) estimation, when compared to current tissues, respectively, at 2% noise with 50 voxels. This standard method - the stoichiometric method based on value can be considered an upper limit as more voxels single-energy CT (SECT). However, a few recent studies and lower noise level rapidly decreased the uncertainty. indicated that imaging noise may have a substantial impact on the performance of the DECT-based approach, Conclusion: especially at a high noise level. The goal of this study is to quantify the uncertainty in SPR and range estimation We have systematically evaluated the impact of noise caused by noise in the DECT-based approach under to the DECT-based SPR estimation and identified under various conditions. various conditions that the variation caused by noise is the dominant uncertainty-contributing component. We Results: conclude that, based on the noise level and tumor depth, it is important to estimate and include the uncertainty Due to the algorithms being nonlinear and/or having due to noise in estimating the overall range uncertainty hard thresholds in the CT number to SPR mapping, noise before implementing a small margin in the range of 1%. in the CT numbers induced a shift in the mean SPR from its noiseless reference SPR. The degree of the mean shift was dependent on the algorithm and tissue type, but its impact on the SPR uncertainty was mostly small compared to the variation. All mean shifts observed in this study were within 0.5% at a noise level of 2%. The ratio of the influence of variation to mean shift was mostly greater than 1, indicating that variation more likely determined the uncertainty caused by noise. https://pubmed.ncbi.nlm.nih.gov/30883827/ CT Dual Energy imaging in Radiation Oncology · Literature overview 51 Publications on CT Dual Energy in Proton Therapy Comprehensive analysis of proton range uncertainties related to stopping-power-ratio estimation using Keywords: dual-energy CT imaging • SOMATOM Force • Dual Source Dual Energy • Author: Li B, Lee HC, Duan X, Shen C, Zhou L, Jia X, Yang M Proton Therapy • Stopping Power Ratio / SPR Department of Radiation Oncology, University of Texas Southwestern • Medical Center, Dallas, USA. (for complete affiliations see online article) Lung • Prostate Date: Aug 2017 • Head and neck Abstract: The dual-energy CT-based (DECT) approach holds promise eventually determined for three tumor sites (lung, prostate in reducing the overall uncertainty in proton stopping- and head-and-neck) by weighting the relative proportion power-ratio (SPR) estimation as compared to the of each tissue group for that specific site. The uncertainties conventional stoichiometric calibration approach. associated with the two selected DECT methods were The objective of this study was to analyze the factors found to be similar, therefore the following results contributing to uncertainty in SPR estimation using applied to both methods. The overall uncertainty (1σ) the DECT-based approach and to derive a comprehensive in SPR estimation with the DECT-based approach was estimate of the range uncertainty associated with SPR estimated to be 3.8%, 1.2% and 2.0% for lung, soft and estimation in treatment planning. Two state-of-the-art bone tissues, respectively. The dominant factor DECT-based methods were selected and implemented contributing to uncertainty in the DECT approach was on a Siemens SOMATOM Force DECT scanner. The the imaging uncertainties, followed by the DECT modeling uncertainties were first divided into five independent uncertainties. Our study showed that the DECT approach categories. The uncertainty associated with each can reduce the overall range uncertainty to approximately category was estimated for lung, soft and bone tissues 2.2% (2σ) in clinical scenarios, in contrast to the previously separately. A single composite uncertainty estimate was reported 1%. https://pubmed.ncbi.nlm.nih.gov/28678019/ 52 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Optimal energy selection for proton stopping-power-ratio estimation using dual-energy CT-based monoenergetic Keywords: imaging • SOMATOM Force • Dual Source Dual Energy • Author: Je E, Lee HH, Duan X, Li B, Jia X, Yang M Proton Therapy • Stopping Power Ratio / SPR Department of Radiation Oncology, University of Texas Southwestern • Medical Center, Dallas, USA (for complete affiliations see online article) Monoenergetic / keV • Stoichiometric calibration Date: Sep 2019 Abstract: The dual-energy computed tomography (DECT)-based associated with each energy; these were then combined approach holds promise in reducing the overall uncertainty into a single composite uncertainty for three tumor sites in proton stopping-power-ratio (SPR) estimation, but (head-and-neck (HN), lung, and prostate). The optimal cannot be easily implemented with most commercial energy was eventually selected based on the composite proton treatment planning systems (TPS). In this study, range uncertainty, which turned out to be 160 keV we revisited the idea of coupling the stoichiometric for both DECT scanners. At 160 keV, the total uncertainties calibration method with virtual monoenergetic CT (2σ) in SPR estimation were determined to be 3.2%-4.5%, datasets (MonoCT) generated by modern DECT scanners, 0.9%, and 1.4%-1.6% for lung, soft, and bony tissues, because of its readiness for implementation with the respectively. These results were comparable to the corres- existing TPS. Our objective was to determine the optimal ponding values estimated for the DECT approach evaluated energy of the MonoCT dataset for stoichiometric in our previous study: 3.8%, 1.2% and 2.0%, for lung, soft, calibration and estimate the overall uncertainty in SPR and bony tissues, respectively. The composite range estimation at the optimal energy. We performed uncertainties (2σ) were estimated as 1.5%, 1.7%, and stoichiometric calibration for MonoCT datasets across 1.5% for prostate, lung, and HN, respectively. Our results the energy range available on a Siemens Force DECT demonstrated the potential of MonoCT images for scanner and a Philips IQon DECT scanner in a 10 keV reducing proton SPR uncertainty. Further clinical studies step. We estimated the uncertainties of different sources are needed to compare this approach with the DECT (imaging, modeling, and inherent uncertainties) for approach directly on real patient cases. different tissue types (lung, soft, and bone tissues) https://pubmed.ncbi.nlm.nih.gov/31437824/ CT Dual Energy imaging in Radiation Oncology · Literature overview 53 Publications on CT Dual Energy in Proton Therapy Validation of proton stopping power ratio estimation based on dual energy CT using fresh tissue samples Keywords: • SOMATOM Force • SOMATOM Definition Edge • Author: Taasti VT, Michalak GJ, Hansen DC, Deisher A, Kruse J, Krauss B, SOMATOM Definition AS Muren L, Petersen J, McCollough C. • SOMATOM Definition Flash • Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark. syngo.via (for complete affiliations see online article) • Dual Spiral Dual Energy • TwinBeam Dual Energy Date: Dec 2017 • Dual Source Dual Energy • Proton Therapy • Stopping Power Ratio / SPR Abstract: Dual energy CT (DECT) has been shown, in theoretical and acquired and SECT-based SPR estimations were performed phantom studies, to improve the stopping power ratio using a clinical Hounsfield look-up table. The mean and (SPR) determination used for proton treatment planning standard deviation of the SPR over large volume-of-interests compared to the use of single energy CT (SECT). However, were calculated. For the six different DECT acquisition it has not been shown that this also extends to organic methods, the root-mean-square errors (RMSEs) for tissues. The purpose of this study was therefore to the SPR estimates over all tissue samples were between investigate the accuracy of SPR estimation for fresh pork 0.9% and 1.5%. For the SECT-based SPR estimation and beef tissue samples used as surrogates of human the RMSE was 2.8%. For one DECT acquisition method, tissues. The reference SPRs for fourteen tissue samples, a positive bias was seen in the SPR estimates, having a which included fat, muscle and femur bone, were mean error of 1.3%. The largest errors were found in measured using proton pencil beams. The tissue samples the very dense cortical bone from a beef femur. This study were subsequently CT scanned using four different confirms the advantages of DECT-based SPR estimation scanners with different dual energy acquisition modes, although good results were also obtained using SECT giving in total six DECT-based SPR estimations for each for most tissues. sample. The SPR was estimated using a proprietary algorithm (syngo.via DE Rho/Z Maps, Siemens Healthcare, Forchheim, Germany) for extracting the electron density and the effective atomic number. SECT images were also https://pubmed.ncbi.nlm.nih.gov/29057753/ 54 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy Keywords: • SOMATOM Force • Biograph mCT • Author: Berndt B, Landry G, Schwarz F, Tessonier T, Kamo F, Dedes G, MAGNETOM Skyra Thieke C, Würl M, Kurz C, Ganswindt U, Verhaegen F, Debus J, Belka C, • Dual Source Dual Energy Sommer W, Reiser M, Bauer J, Parodi K. • PET/CT Department of Medical Physics, Ludwig-Maximilians-Universität München, • MRI Germany. (for complete affiliations see online article) • Proton Therapy • Range verification Date: Feb 2017 • Brain segmentation • Tissue substitutes Abstract: The purpose of this work was to evaluate the ability of and post-treatment PET scans was investigated. For BES, single and dual energy computed tomography (SECT, DECT) DECTdist and SECTdist reduced differences to the reference to estimate tissue composition and density for usage in simulation by up to 62% when compared to the Monte Carlo (MC) simulations of irradiation induced conventional stoichiometric segmentation (SECTSchneider). β + activity distributions. This was done to assess the In comparison to MR brain segmentation, Dice similarity impact on positron emission tomography (PET) range coefficients for WM, GM and CSF were 0.61, 0.67 and verification in proton therapy. A DECT-based brain tissue 0.66 for DECTdist and 0.54, 0.41 and 0.66 for SECTdist. segmentation method was developed for white matter MC simulations of PET treatment verification in patients (WM), grey matter (GM) and cerebrospinal fluid (CSF). showed important differences between DECTdist/SECTdist The elemental composition of reference tissues was and SECTSchneider for patients with large CSF areas within assigned to closest CT numbers in DECT space (DECTdist). the treatment field but not in WM and GM. Differences The method was also applied to SECT data (SECTdist). could be misinterpreted as PET derived range shifts of In a validation experiment, the proton irradiation induced up to 4 mm. DECTdist and SECTdist yielded comparable PET activity of three brain equivalent solutions (BES) activity distributions, and comparison of SECTdist to a was compared to simulations based on different tissue measured patient PET scan showed improved agreement segmentations. Five patients scanned with a dual source when compared to SECTSchneider. The agreement between DECT scanner were analyzed to compare the different predicted and measured PET activity distributions was segmentation methods. A single magnetic resonance improved by employing a brain specific segmentation (MR) scan was used for comparison with an established applicable to both DECT and SECT data. segmentation toolkit. Additionally, one patient with SECT https://pubmed.ncbi.nlm.nih.gov/28182581/ CT Dual Energy imaging in Radiation Oncology · Literature overview 55 Publications on CT Dual Energy in Proton Therapy Ex vivo validation of a stoichiometric dual energy CT proton stopping power ratio calibration Keywords: • SOMATOM Sensation Open • Dual Source Dual Energy • Author: Xie Y, Ainsley C, Yin L, Zou W, McDonough J, Solberg T, Lin A, Teo B. Proton Therapy • Stopping Power Ratio / SPR Department of Radiation Oncology, University of Pennsylvania, • Philadelphia, USA. (for complete affiliations see online article) Single energy CT SPR calibration • Dual energy CT SPR calibration Date: Mar 2018 • Beam hardening Abstract: A major source of uncertainty in proton therapy is the irradiation. Ex vivo validation was performed using five conversion of Hounsfield unit (HU) to proton stopping different types of frozen animal tissues with the MLIC and power ratio relative to water (SPR). In this study, we three types of fresh animal tissues using film. In addition, measured and quantified the accuracy of a stoichiometric the residual ranges recorded on the film were used to dual energy CT (DECT) SPR calibration. We applied a compare with those from the treatment planning system stoichiometric DECT calibration method to derive the SPR using both DECT and SECT derived SPRs. Bland-Altman using CT images acquired sequentially at 80kVp and analysis indicates that the differences between DECT and 140kVp. The dual energy index was derived based on the SPR measurement of tissue surrogates, frozen and fresh HUs of the paired spectral images and used to calculate animal tissues has a mean of 0.07% and standard the effective atomic number (Z eff), relative electron deviation of 0.58% compared to 0.55% and 1.94% density (ρe), and SPRs of phantom and biological respectively for single energy CT (SECT) and SPR measure- materials. Two methods were used to verify the derived ment. Our ex vivo study indicates that the stoichiometric SPRs. The first method measured the sample’s water DECT SPR calibration method has the potential to be more equivalent thicknesses to deduce the SPRs using a multi- accurate than SECT calibration under ideal conditions layer ion chamber (MLIC) device. The second method although beam hardening effects and other image utilized Gafchromic EBT3 film to directly compare relative artifacts may increase this uncertainty. ranges between sample and water after proton pencil beam https://pubmed.ncbi.nlm.nih.gov/29513647/ 56 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy Dosimetric comparison of stopping power calibration with dual-energy CT and single-energy CT in proton Keywords: therapy treatment planning • Proton Therapy • Stopping Power Ratio / SPR • Author: Zhu J, Penfold SN. Calibration accuracy • Dosimetric calculations Department of Physics, University of Adelaide, Australia. (for complete affiliations see online article) Date: Jun 2016 Purpose: Results: The accuracy of proton dose calculation is dependent on SPR calculation accuracy was found to be superior, on the ability to correctly characterize patient tissues with average, with DECT relative to SECT. Maximum errors medical imaging. The most common method is to correlate of 12.8% and 2.2% were found for SECT and DECT, computed tomography (CT) numbers obtained via single- respectively. Qualitative examination of dose difference energy CT (SECT) with proton stopping power ratio (SPR). maps clearly showed the dosimetric advantages of DECT CT numbers, however, cannot discriminate between imaging, compared to SECT imaging for IMPT dose a change in mass density and change in chemical calculation for the case investigated. Quantitatively, the composition of patient tissues. This limitation can have maximum dose calculation error in the SECT plan was 7.8%, consequences on SPR calibration accuracy. Dual-energy compared to a value of 1.4% in the DECT plan. When CT (DECT) is receiving increasing interest as an alternative considering the high dose target region, the root mean imaging modality for proton therapy treatment planning square (RMS) error in dose calculation was 2.1% and 0.4% due to its ability to discriminate between changes in patient for SECT and DECT, respectively. density and chemical composition. In the current work we use a phantom of known composition to demonstrate Conclusion: the dosimetric advantages of proton therapy treatment planning with DECT over SECT. DECT-based proton treatment planning in a commercial treatment planning system was successfully demonstrated for the first time. DECT is an attractive imaging modality for proton therapy treatment planning owing to its ability to characterize density and chemical composition of patient tissues. SECT and DECT scans of a phantom of known composition have been used to demonstrate the dosimetric advantages obtainable in proton therapy treatment planning with DECT over the current approach based on SECT. https://www.ncbi.nlm.nih.gov/pubmed/27277033 CT Dual Energy imaging in Radiation Oncology · Literature overview 57 Publications on CT Dual Energy in Proton Therapy Status and innovations in pre-treatment CT imaging for proton therapy Keywords: • Proton Therapy • Dose conformality • Author: Wohlfahrt P, Richter C. Stopping Power Ratio / SPR • Stopping-power prediction Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. National Center for Radiation Research in Oncology, Technische Universität Dresden, Dresden, Germany. (for complete affiliations see online article) Date: Mar 2020 Abstract: Pre-treatment CT imaging is a topic of growing importance in particle therapy. Improvements in the accuracy of stopping-power prediction are demanded to allow for a dose conformality that is not inferior to state-of-the-art image-guided photon therapy. Although range uncertainty has been kept practically constant over the last decades, recent technological and methodological developments, like the clinical application of dual-energy CT, have been introduced or arise at least on the horizon to improve the accuracy and precision of range prediction. This review gives an overview of the current status, summarizes the innovations in dual-energy CT and its potential impact on the field as well as potential alternative technologies for stopping-power prediction. https://www.ncbi.nlm.nih.gov/pubmed/31642709 58 Literature overview · CT Dual Energy imaging in Radiation Oncology Publications on CT Dual Energy in Proton Therapy A comparison study between single- and dual-energy CT density extraction methods for neurological proton Keywords: Monte Carlo treatment planning • Dual Source Dual Energy • Dual Spiral Dual Energy • Author: Van der Heyden B, Almeida I, Vilches-Freicas G, van Beveren C, DirectDensity Vaniqui A, Ares C, Terhaag K, Fonesca G, Eekers D, Verhaegen F. • Proton Therapy • Department of Radiation Oncology (MAASTRO), Relative electron densities Maastricht University Medical Centre, the Netherlands. • OAR contouring (for complete affiliations see online article) • Brain tumors Date: Oct 2019 Purpose: Conclusion: Monte Carlo proton dose calculations requires mass Given the wide choice of available conversion methods, densities calculated from the patient CT image. This work studies investigating the density accuracy for proton investigates the impact of different single-energy CT dose calculations are necessary. However, there is still (SECT) and dual-energy CT (DECT) to density conversion a gap between performing accuracy studies in reference methods in proton dose distributions for brain tumours. ρe phantoms and applying these methods in human CT images. For this treatment case, the PMI2RED method Results: was equivalent to the conventional CT2RED method in In the phantom study, Saito-15it and Hünemohr-15it terms of dose distribution, CTV coverage and OAR produced the lowest ρe root-mean-square error (0.7%) sparing, whereas Hünemohr-15it and Saito-15it and DirectDensity™ the highest error (2.7%). The proton presented the largest differences. plan evaluated in the Saito-15it and Hünemohr-15it datasets showed the largest relative differences compared to initial CT2RED plan down to −6% of the prescribed dose. Compared to CT2RED, average range differences were calculated: −0.1 ± 0.3 mm for PMI2RED; −0.8 ± 0.4 mm for Hünemohr-15it, and −1.2 ± 0.4 mm for Saito-15it. https://pubmed.ncbi.nlm.nih.gov/31646923/ CT Dual Energy imaging in Radiation Oncology · Literature overview 59 Siemens Healthineers Headquarters Siemens Healthcare GmbH Henkestr. 127 91052 Erlangen, Germany Phone: +49 9131 84-0 siemens-healthineers.com Published by Siemens Healthcare GmbH · Digital only · 9434 1120 · ©Siemens Healthcare GmbH, 2020

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